Chronic pain: Journals & articles

Abstract
Objectives: Spinal cord stimulation (SCS) therapy is an effective treatment for chronic pain, particularly in conditions such as postlaminectomy syndrome and complex regional pain syndrome (CRPS). Rare case reports described significant weight loss in patients who underwent dorsal column SCS therapy for chronic pain. Recently, neuromodulation for obesity has become a novel field for research. We aimed to investigate weight trends among patients treated with SCS for chronic pain.

Materials and methods: We conducted a retrospective chart review in 342 patients treated with SCS or dorsal root ganglion stimulators at our institution between 2010 and 2023. Patients had their weight recorded before SCS implantation and at least once within 12 months after surgery. We also conducted interviews with 28 patients who experienced significant weight loss or had revision procedures owing to weight loss.

Results: We found that 105 of 342 patients (30.7%) experienced weight loss of ≥5% within a year of implantation, and 32 of 105 (30.5%, 9.4% of all patients) experienced weight loss of ≥ 10%. A multivariate regression analysis revealed a modest increase in the likelihood of weight loss among patients with CRPS (odds ratio [OR] = 1.17, 95% CI [1.04, 1.30], p = 0.007) and in those who achieved pain relief after implantation (OR = 1.22, 95% CI [1.05,1.40], p = 0.008). Of the 28 patients with significant weight loss who were interviewed, 12 (43%) could not explain the reasons for their weight loss, whereas eight (29%) reported decreased appetite. Leads placed at higher thoracic levels were associated with increased rates of weight loss (37.2% at T6-T8 and 22.3% at T8-T10; p = 0.038).

Conclusions: Our findings suggest that SCS therapy may affect weight in patients with chronic pain. Further studies are needed to investigate the potential role of SCS in weight modulation.

Abstract
Objectives: Raynaud's phenomenon (RP) is a vascular disorder characterized by episodic peripheral artery vasospasms, resulting in paleness, cyanosis, and/or erythema. There are few reports, mostly case reports, on the benefits of spinal cord stimulation (SCS) for the treatment of RP. However, there is a lack of objective evidence on SCS-induced modulation of the sympathetic system (eg, vasodilation) in this condition. We hypothesize that evoked compound action potential-controlled closed-loop SCS may relieve pain, reduce the severity and frequency of Raynaud attacks, and improve peripheral blood flow.

Materials and methods: This prospective, observational, single-center pilot study aimed to evaluate the effectiveness of SCS in treating primary and secondary RP. Patient outcomes such as pain, Raynaud severity/condition score, Cochin Hand Function Scale, Scleroderma Health Assessment Questionnaire RP visual analog scale, EQ-5D-5L, Patient Global Impression of Change, blood flow assessments, and neurophysiological measurements were collected at baseline, trial end, one month, three months, and six months.

Results: Ten patients were successfully enrolled in the study and underwent epidural electrode placement for SCS. SCS resulted in a significant improvement in the severity of RP attacks (severity difference from baseline at trial end: -1.8, 95% CI, -3.1 to -0.5; p = 0.01; at one month: -2.1; 95% CI, -3.4 to -0.8; p = 0.004; at three months: -2.9; 95% CI, -4.2 to -1.6; p = 0.0002) and Raynaud condition score (difference from baseline at trial end: -2.1; 95% CI, -3.3 to -0.9; p = 0.002; at one month: -2.2; 95% CI, -3.4 to -1.0; p = 0.002; at three months: -3.3; 95% CI, -4.6 to -2.1; p = 0.00002; at six months: -4.1; 95% CI, -5.4 to -2.8; p = 0.0000008), and an objective reduction in peripheral occlusion and ulceration. While one of the combined primary end points was successfully achieved in terms of severity at the three-month follow-up, it is worth noting that the primary end point related to frequency improvement was not met during the same time frame.

Conclusions: This pilot study offers evidence linking SCS with the activation of large, myelinated fibers within the dorsal column in patients with RP. This activation is associated with improvement in the number of patient-related outcomes and enhanced peripheral circulation.

Abstract
Objectives: The aim of this systematic review and meta-analysis was to evaluate the effectiveness of the percutaneous electrical stimulation in the modulation of pain and its implication in the function of patients with a painful knee condition.

Methods: A search was conducted from database inception to September 2023 across PubMed, Web of Science and Scopus databases. Randomized controlled trials were included. Two reviewers performed independent data extraction and methodologic quality assessment of the studies. Study quality was assessed using the PEDro scale and the risk of bias was evaluated with the Cochrane Assessment tool.

Results: Eight studies were included. A significant statistical effect was found (P<0.001) for reducing pain and improving function after treatment. Additionally, a significant statistical effect was presented for reducing pain (P=0.009) and improving function (P<0.001) after follow-up. The risk of bias was low.

Conclusion: This review showed a positive effect of applying the percutaneous electrical stimulation reducing pain and improving function in adults with a painful knee.

Abstract
It is known that smoking is associated with greater chronic pain. However, little is known about the magnitude of this relationship and its association with prescription opioid use. We examine the association between smoking status and three sets of outcomes: (1) starting and discontinuing opioids, (2) intensity of opioid use, and (3) opioid use and pain outcomes after quitting smoking. We use multinomial logit on adults in the nationally representative 2013-2021 Medical Expenditure Panel Survey linked to the National Health Interview Survey (N = 36,796). Smoking adults made up 16% of the population but used 30% of all opioid prescriptions and 40% of all annual Morphine Milligram Equivalents (MMEs). The 1% of the population that smoked and had severe work limitations due to pain used 20% of all MMEs. Smoking adults were 24% more likely than never-smoking adults to have chronic pain. Among those with pain, smoking adults had 46% higher relative risk of starting opioids compared to never-smoking adults (p < .01), and smoking adults had 6.6 times higher relative risk of continuing opioids the next year compared to never-smoking adults (p < .01). Those smoking and using opioids had 95% higher odds of using a prescribed dosage of 50 MME or more than never-smoking adults. A year after quitting smoking, opioid use declined by 20% and pain declined by 7% compared to those continuing to smoke, with no difference from never-smoking adults after 12 years. Integrating smoking cessation into pain management programs could be highly beneficial to adults with chronic pain. PERSPECTIVE: Rarely are smoking cessation and pain management programs integrated together. We show that such integration would be highly beneficial by estimating a strong association between smoking cessation and reduced chronic pain, work limitations, and prescription opioid use.

Abstract
The role of the complement system in pain syndromes has garnered attention on the back of preclinical and clinical evidence supporting its potential as a target for new analgesic pharmacotherapies. Of the components that make up the complement system, component 5a (C5a) and component 3a (C3a) are most strongly and consistently associated with pain. Receptors for C5a are widely found in immune resident cells (microglia, astrocytes, sensory neuron-associated macrophages (sNAMs)) in the central nervous system (CNS) as well as hematogenous immune cells (mast cells, macrophages, T-lymphocytes, etc.). When active, as is often observed in chronic pain conditions, these cells produce various inflammatory mediators including pro-inflammatory cytokines. These events can trigger nervous tissue inflammation (neuroinflammation) which coexists with and potentially maintains peripheral and central sensitization. C5a has a likely critical role in initiating this process highlighting its potential as a promising non-opioid target for treating pain. This review summarises the most up-to-date research on the role of the complement system in pain with emphasis on the C5 pathway in peripheral tissue, dorsal root ganglia (DRG) and the CNS, and explores advances in complement-targeted drug development and sex differences. A perspective on the optimal application of different C5a inhibitors for different types (e.g., neuropathic, post-surgical and chemotherapy-induced pain, osteoarthritis pain) and stages (e.g., acute, subacute, chronic) of pain is also provided to help guide future clinical trials. PERSPECTIVE: This review highlights the role and mechanisms of complement components and their receptors in physiological and pathological pain. The potential of complement-targeted therapeutics for the treatment of chronic pain is also explored with a focus on C5a inhibitors to help guide future clinical trials.

Abstract
Objective: Chronic pain in adolescents and young adults (AYAs) is associated with adverse functional and psychological outcomes; however, inconsistent findings across studies necessitate a comprehensive synthesis. This meta-analysis aimed to quantify associations between anxiety, depression, and pain/functional outcomes, and explore study and sample moderators, such as age, sex, pain duration, recruitment setting, and measurement tools.

Methods: We searched MEDLINE, PsycINFO, CENTRAL, and Embase through May 2024. included 57 studies (N = 12,603) of AYAs aged 12-25 years with chronic pain. Risk of bias and GRADE assessments were conducted. Pearson r correlations were meta-analyzed using a random-effects model.

Results: Small associations were found between anxiety, depression, and heightened pain intensity (r = 0.20, 0.24). Moderate-to-large associations were observed between anxiety, depression, and disability (r = 0.32, 0.34), pain interference (r = 0.47, 0.51), pain catastrophizing (both r = 0.50), and poorer quality of life (r = -0.56, -0.61). Anxiety had stronger correlations with pain intensity and catastrophizing in samples with more males. Anxiety measure moderated the anxiety-pain intensity relationship. Depression had stronger correlations with pain intensity for shorter pain duration, and catastrophizing and pain interference for longer pain durations. The depression-catastrophizing association was stronger in older samples.

Conclusion: Anxiety and depression significantly impact the chronic pain experience in AYAs, with stronger effects on functional outcomes and quality of life than pain intensity. Tailored interventions that consider age, sex, and pain duration may enhance treatment outcomes in this population.

Abstract
Introduction: During the last decade, the complementary value of real-world data (through registries or medical records) and data from randomized clinical trials has been recognized as increasingly important. In the field of neuromodulation, only a few industry-independent nationwide neuromodulation registries are available. The interest in creating a European registry has increased but without a successful result. The goal of this online survey is to gain further insights into the need for and burden of a European registry for neuromodulation.

Materials and methods: An online survey was developed and distributed during the 3rd Joint Congress of the International Neuromodulation Society European Chapters in September 2023 (Hamburg, Germany). Healthcare professionals were asked to indicate the need for a European registry, the items that should be collected, and the restrictions to access of a European registry.

Results: In total, 125 respondents opened the link to the survey, of whom 104 completed (at least partly) the survey. Of the 104 responses, 91% indicated that there is a need for a European registry, whereas 6% indicated there is no need. The main reasons for establishing a registry on a European level were the possibility of collecting real-world evidence (84%), the potential to collect big data from European patients (82%), to evaluate safety in neuromodulation (70%), and the possibility of reporting yearly on European activity in neuromodulation (51%). Indications for neuromodulation, patient characteristics, and follow-up assessments were most often stated as items that should be collected. Access should not only be granted to implanters but also to nurses, the assessment team, and other physicians, as agreed on by 64%, 52%, and 51%, respectively.

Discussion: More than 90% of the respondents believed that a European registry for neuromodulation is needed, mainly to obtain real-world (big) data about the effectiveness and safety of this therapy. This survey clearly pointed to the need for a European registry for which it seems key to ensure financial and logistical support, in addition to in-depth legal guidance in developing this registry.

Abstract
Objectives: Non-malignant chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in chronic non-malignant pain patients using quantitative sensory testing (QST) and quality of life questionnaires: (1) Brief Pain Inventory-short form (BPI-sf), (2) European Organization for Research and Treatment of Life Questionnaire (EORTC-C30), and (3) Hospital Anxiety Depression Scale (HADS).

Methods: Eleven non-malignant chronic pain patients (51±13.6 years old, 5M) participated in the study. Anodal tDCS was applied for five consecutive days, followed by sham stimulation after a washout period of at least two weeks. Pressure pain thresholds (PPT) and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5.

Results: Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT (P=0.007). Additionally, anodal tDCS increased PTT compared to sham at day 5 at Th10 ventral dermatomes (P=0.014). Both anodal and sham tDCS decreased the BPI-sf total and interference scores, and the EORTC-C30 fatigue score, but no interaction effect was observed.

Discussion: This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of non-malignant chronic pain.

Abstract
Chronic pain is common among children and adolescents; however, the diagnoses in the newly developed 11th revision of the International Classification of Diseases (ICD-11) chronic pain chapter are based on adult criteria, overlooking pediatric neurodevelopmental differences. The chronic pain diagnoses have demonstrated good clinical applicability in adults, but to date, no field study has examined these diagnoses to the most specific diagnostic level in a pediatric sample. The current study aimed to explore pediatric representation within the ICD-11, with focus on chronic primary pain. Healthcare professionals (HCPs) at a specialized pediatric pain center documented the symptoms of and assigned both ICD-10 and ICD-11 diagnoses to N = 402 patients. Using criteria-based computer algorithms, specific ICD-11 pain diagnoses were allocated for each documented pain location, with residual diagnoses (ie, "unspecified") assigned if criteria were not (fully) met. Within the ICD-11, the algorithms assigned specific pain diagnoses to most patients (73.6%). In ICD-10, HCPs could not specify a diagnosis for 5.2% of patients; the ICD-11 algorithm allocated a residual chronic primary pain diagnosis in 51.2%. Residual categories were especially prevalent among younger children, boys, patients with headaches, and those with lower pain severity. Overall, clinical utility of the ICD-11 was high, although less effective for chronic back pain and headache diagnoses. The latter also exhibited the lowest agreement between HCPs and algorithm. The current study underscores the need for evidence-based improvements to the ICD-11 diagnostic criteria in pediatrics. Developing pediatric coding notes could improve the visibility of patients internationally and improve the likelihood of receiving reimbursement for necessary treatments through accurate coding.

Abstract
Objectives: Neuromodulation is an effective treatment for chronic pain; however, socioeconomic differences may influence decision-making to initiate this therapy. This review investigated potential differences in accessibility of neuromodulation for patients with chronic pain due to socioeconomic determinants.

Materials and methods: Four electronic databases were used for this systematic review: MEDLINE, Embase, Scopus, and Web of Science. Risk of bias was assessed using the modified version of the Downs and Black checklist. The study protocol was prospectively registered on PROSPERO (CRD42023426035).

Results: The initial database search identified a total of 1118 unique studies, of which 36 were eventually included in the systematic review. Of the 36 included studies, six studies reported on education, 24 on employment status, ten on insurance, five on household income, and three on miscellaneous topics. Neuromodulation seems accessible for patients with different education levels and different types of insurance. Additionally, it is not restricted to patients who are (un)employed. When comparing patients who initiated neuromodulation with those who did not, a significantly higher number of patients in the top quartile for education were found in the group without neuromodulation. Regarding insurance, inconclusive evidence was found.

Conclusions: Although neuromodulation was accessible for patients with varying levels of socioeconomic determinants, disparities were noted. When comparing the socioeconomic profiles of patients who receive neuromodulation and those who do not, education levels differ. Health-related inequality should be carefully monitored in chronic pain management with neuromodulation to ensure that potential disparities do not increase.

Abstract
Background: Whether regional anesthesia impacts the development of chronic postsurgical pain is currently debateable, and few studies have evaluated an effect on prolonged opioid use. We sought to systematically review the effect of regional anesthesia for adults undergoing noncardiac elective surgery on these outcomes.

Methods: A systematic search was conducted in MEDLINE, EMBASE, CENTRAL, and CINHAL for randomized controlled trials (from inception to April 2022) of adult patients undergoing elective noncardiac surgeries that evaluated any regional technique and included one of our primary outcomes: (1) prolonged opioid use after surgery (continued opioid use ≥2 months postsurgery) and (2) chronic postsurgical pain (pain ≥3 months postsurgery). We conducted a random-effects meta-analysis on the specified outcomes and used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to rate the quality of evidence.

Results: Thirty-seven studies were included in the review. Pooled estimates indicated that regional anesthesia had a significant effect on reducing prolonged opioid use (relative risk [RR] 0.48, 95% CI, 0.24-0.96, P = .04, I2 0%, 5 trials, n = 348 patients, GRADE low quality). Pooled estimates for chronic pain also indicated a significant effect favoring regional anesthesia at 3 (RR, 0.74, 95% CI, 0.59-0.93, P = .01, I2 77%, 15 trials, n = 1489 patients, GRADE moderate quality) and 6 months (RR, 0.72, 95% CI, 0.61-0.85, P < .001, I2 54%, 19 trials, n = 3457 patients, GRADE moderate quality) after surgery. No effect was found in the pooled analysis at 12 months postsurgery (RR, 0.44, 95% CI, 0.16-1.17, P = .10).

Conclusions: The results of this study suggest that regional anesthesia potentially reduces chronic postsurgical pain up to 6 months after surgery. Our findings also suggest a potential decrease in the development of persistent opioid use.

Abstract
Postoperative lingual nerve injury is a rare but serious complication following airway management and can lead to significant discomfort and disability. This literature review explores the aetiology, clinical presentation, management strategies and potential preventive measures for lingual nerve injuries associated with airway management during surgery. A search of PubMed, MEDLINE, EMBASE Science Direct, Cochrane library and Web of Science databases was done since inception to January 2024, including any observational studies and clinical trials describing patients diagnosed with lingual nerve injury following airway instrumentation. Multiple risk factors for lingual nerve injury were identified. Anaesthesia factors include difficulty with intubation and use of laryngeal mask airway. Surgical factors are long duration of operation and surgery of the head and neck. Patient factor includes female sex. Anaesthetists should proactively inform patients about the potential for this nerve injury and control modifiable risk factors to mitigate the risk of injury.

Abstract
Introduction: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications.

Materials and methods: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures.

Results: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions.

Conclusions: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements.

Abstract
Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture group or sham acupuncture group and received 10 sessions of treatment during 4 weeks. The Visual Analog Scale (VAS) for leg pain, Oswestry Disability Index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression (SVR) analyses were performed. Compared to sham acupuncture, acupuncture significantly improved symptoms, including VAS for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus (PoCG). Furthermore, the actual 4-week ODI values were positively correlated with the SVR predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right PoCG may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain.

Abstract
Objective: Chronic pain is known to be an important construct in clinical practice and a particular form of chronic pain, high-impact chronic pain (HICP), has gained recent interest and attention by pain clinicians, epidemiologists, and clinical researchers. The purpose of our Topical Review is to describe the historical development of measures of HICP and to explore the psychometric properties of HICP as well as to present alternative measurement methods.

Methods: We identified strengths and weaknesses of the psychometric characteristics of HICP measures. Limitations of existing HICP measures were discussed and summarized and alternatives to current methods were proposed.

Results: HICP operational definitions show variability across studies. All definitions cannot be correct, but which ones are incorrect cannot be determined as there is no gold standard. Random measurement error and recall bias are among the other limitations of current HICP measures. Model-based definitions of HICP, the discrete (for epidemiologic applications) and continuous (for clinical applications) latent variable models are discussed as likely superior alternatives to current methods.

Conclusions: Limitations of existing HICP methods are discussed and alternative development approaches to HICP measures are presented. The use of either discrete or continuous latent variable models would improve upon the psychometric characteristics of current HICP evidence. Examples are used to illustrate the benefits of latent variable models over traditional observed variable conceptualizations as the measurement of HICP continues to develop.

Significance statement: This work takes the position that current methods of measuring high impact chronic pain (HICP) likely contain substantial error. We have endorsed an alternative approach for several psychometrically grounded reasons. We recommend that future work consider the discrete latent variable framework for dichotomous measures of HICP and the continuous latent variable framework for continuous measures of HICP. The paper provides illustrative examples of these methods for a different patient reported measure that is lacking a gold standard, much like HICP measures.

Abstract
Complex regional pain syndrome (CRPS) presents postinjury with disproportionate pain and neuropathic, autonomic, motor symptoms, and skin texture affection. However, the origin of these multiplex changes is unclear. Skin biopsies offer a window to analyze the somatosensory and vascular system as well as skin trophicity with their protecting barriers. In previous studies, barrier-protective exosomal microRNAs were altered in CRPS. We here postulated that tissue architecture and barrier proteins are already altered at the beginning of CRPS. We analyzed ipsilateral and contralateral skin biopsies of 20 fully phenotyped early CRPS patients compared with 20 age- and sex-matched healthy controls. We established several automated unbiased methods to comprehensively analyze microvessels and somatosensory receptors as well as barrier proteins, including claudin-1, claudin-5, and claudin-19. Meissner corpuscles in the skin were bilaterally reduced in acute CRPS patients with some of them lacking these completely. The number of Merkel cells and the intraepidermal nerve fiber density were not different between the groups. Dermal papillary microvessels were bilaterally less abundant in CRPS, especially in patients with allodynia. Barrier proteins in keratinocytes, perineurium of dermal nerves, Schwann cells, and papillary microvessels were not affected in early CRPS. Bilateral changes in the tissue architecture in early CRPS might indicate a predisposition for CRPS that manifests after injury. Further studies should evaluate whether these changes might be used to identify risk patients for CRPS after trauma and as biomarkers for outcome.

Abstract
Objectives: Chronic pain poses a significant health challenge worldwide and is associated with both disability and reduced quality of life. Sleep disturbances are reported in 67% to 88% of patients with chronic pain. Pain and sleep affect each other reciprocally; we aimed to study this bidirectional relationship in patients treated with spinal cord stimulation (SCS) for chronic pain. Specifically, we investigated whether sleep improves after treatment with SCS and whether this improvement may be mediated by pain reduction.

Materials and methods: An observational cohort study was conducted in patients with chronic neuropathic pain treated with SCS at a single neurosurgical department in Denmark. Outcomes were assessed preoperatively and at three, six, and 12 months postoperatively, and thereafter annually. Primary outcomes were pain intensity (numeric rating scale) and insomnia at first follow-up (Insomnia Severity Index). The association between sleep and pain was investigated using linear regression and mediation analysis.

Results: Forty-three patients were included in the study. The mean insomnia score was reduced by 25% from 18.1 (SD 6.0) to 13.5 (SD 6.6) (p = 0.0001). Pain intensity was reduced 38% from 7.4 (SD 1.6) to 4.6 (SD 2.1) at the first follow-up (p ≤ 0.0001). Changes in pain and changes in insomnia scores were significantly but weakly associated (regression coefficient = 1.3, 95% CI [0.3; 2.2], p = 0.008, r2 = 15.7%); and changes in pain score were not found to mediate changes in sleep score (β = -0.02, 95% CI [-0.15; 0.11], p = 0.76).

Conclusions: We found that patients treated with SCS showed significant improvements in both insomnia and pain intensity at first follow-up. Improvements in insomnia and pain intensity were significantly but weakly associated, and improvements in pain intensity score did not mediate improvements in insomnia score. Thus, improvements in self-reported insomnia in patients treated with SCS for chronic pain may predominantly be caused by other factors than reduced pain intensity.

Keywords: Chronic pain; insomnia; pain management; sleep; spinal cord stimulation.

Abstract
Pain is an interpersonal and inherently social experience. Pain perception and administration of medical treatment all occur in a particular environmental and social context. Early environmental influences, and early learning experiences and interactions, condition the body's response to different threats (like pain), ultimately shaping the underlying neurophysiology. These early interactions and experiences also determine what situations are perceived as threatening, as well as our belief in our own ability to self-manage, and our belief in others to offer support, during perceived threats. These beliefs intrinsically drive the combination of behaviours that emerge in response to perceived threats, including pain. Such behaviours can be categorised into attachment styles. In this interdisciplinary review, we synthesise and summarise evidence from the neurobiological, psychobiological, psychosocial and psychobehavioural fields, to describe how these beliefs are embedded in the brain's prediction models to generate a series of expectations/perceptions around the level of safety/threat in different contexts. As such, these beliefs may predict how one experiences, and responds to, pain; with potentially significant implications for the development and management of chronic pain. Little attention has been directed to the effect of adult attachment style on pain in research studies and in the clinical setting. Using interdisciplinary evidence, we argue why we think this interaction merits further consideration and research. PERSPECTIVE: This review explores the influence of attachment styles on pain perception, suggesting a link between social connections and chronic pain development. It aligns with recent calls to emphasise the social context in pain research and advocates for increased focus on adult attachment styles in research and clinical practice.

Abstract
Numerous genome-wide association studies have identified risk genes for chronic pain, yet the mechanisms by which genetic variants modify susceptibility have remained elusive. We sought to identify key genes modulating chronic pain risk by regulating brain protein expression. We integrated brain proteomic data with the largest genome-wide dataset for multisite chronic pain (N=387,649) in a proteome-wide association study (PWAS) using discovery and confirmatory proteomic datasets (N=376 and 152) from the dorsolateral prefrontal cortex (dPFC). Leveraging summary data-based Mendelian randomization (SMR) and Bayesian colocalization analysis (COLOC), we pinpointed potential causal genes, while a transcriptome-wide association study (TWAS) integrating 452 human brain transcriptomes investigated whether cis-effects on protein abundance extended to the transcriptome. Single-cell RNA sequencing data and single-nucleus transcriptomic data revealed cell-type specific expression patterns for identified causal genes in the dPFC and dorsal root ganglia (DRG), complemented by RNA microarray analysis of expression profiles in other pain-related brain regions. Of the 22 genes cis-regulating protein abundance identified by the discovery PWAS, 18 (82%) were deemed causal by SMR or COLOC analyses, with 7 of these 18 genes (39%) replicating in the confirmatory PWAS, including GMPPB, which also associated at the transcriptome level. Several causal genes exhibited selective expression in excitatory neurons, inhibitory neurons, oligodendrocytes, and astrocytes, while most identified genes were expressed across additional pain-related brain regions. This integrative proteogenomic approach identified 18 high-confidence causal genes for chronic pain, regulated by cis-effects on brain protein levels, suggesting promising avenues for treatment research and indicating a contributory role for the DRG. PERSPECTIVE: The current post-GWAS analyses identified 18 high-confidence causal genes regulating chronic pain risk via cis-modulation of brain protein abundance, suggesting promising avenues for future chronic pain therapies. Additionally, the significant expression of these genes in the DRG indicated a potential contributory role, warranting further investigation.

Abstract
Background: The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP.

Methods: This 4-year longitudinal study examined data from an exhaustive acute care hospital register on home-dwelling older adult patients (≥65) with polypharmacy. Commonly known combinations of potentially inappropriate medications were used to estimate therapy adequacy. Patient complexity was evaluated by comparing number of comorbidities and investigating physical and cognitive deficits.

Results: We determined a prevalence of CNCP of 9.7% among all older adult inpatients with polypharmacy, rising to 11.3% for those aged ≥85. Overall, CNCP patients were prescribed more drugs and had more comorbidities and physical and cognitive deficits than patients without CNCP. Older adult patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics and elevated opioid dosages. Older adult patients with CNCP aged ≥85 received fewer analgesics, opioids, non-steroidal anti-inflammatory drugs and co-analgesics but more paracetamol. Older adult patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid.

Conclusion: Observed differences in medication use between older adult inpatients with or without CNCP may be relevant for clinical practice. Potentially inadequate co-prescribing (such as hypnotics and opioids) affects a higher proportion of patients with CNCP and may have serious unintended consequences.

Significance statement: This study describes differences in prescription patterns between people with and without chronic non-cancer pain in a large dataset of 20,422 discharges. The differences found may be relevant to clinical practice. In particular, high co-prescribing of opioids and hypnotics may have serious unintended consequences. Greater physical and cognitive deficits may indicate greater patient complexity, and appropriate interventions need to be developed to improve the management of this vulnerable patient group.

Abstract
Background: Chronic pain is associated with depression and anxiety symptoms. Pain management programms, delivered face-to-face or via the internet, can effectively help adults manage the impacts of chronic pain. Sudden gains are defined as substantial, rapid, and lasting symptom reductions that occur between consecutive treatment sessions and have been associated with better treatment outcomes in non-pain samples. This study examined whether adults with chronic pain report sudden gains in depression or anxiety symptoms during an 8-week online pain management programme, and whether sudden gains were associated with better treatment outcomes for depression or anxiety. Dominant theories of sudden gains argue that therapists are required for sudden gains to be maintained and improve treatment outcomes.

Methods: Using data from a published randomized controlled trial (n = 338), sudden gains and treatment outcomes were compared across three levels of therapist guidance provided alongside the programme: weekly, optional, and self-guided.

Results: Similar rates of sudden gains were observed in depression (22%) and anxiety (24%) across the treatment period, and most sudden gains occurred between Weeks 1 and 2 of treatment. Therapist guidance was not associated with sudden gains; higher baseline symptom severity emerged as the only consistent predictor of sudden gain status. No significant differences in treatment outcomes for depression or anxiety symptoms between sudden gainers and non-gainers were observed across therapist guidance conditions.

Conclusions: These results do not support an association between sudden gains in depression or anxiety symptoms and better post-treatment outcomes, at least for adults with chronic pain.

Significance statement: Sudden gains in depression and anxiety symptoms were not associated with improved treatment outcomes for adults with chronic pain who participated in an online pain management programme, regardless of the level of therapist guidance provided. These findings suggest possible differences in symptom change in chronic pain samples compared to general population samples.

Abstract
Background: There is clear evidence demonstrating the benefits of physical activity (PA) on pain and overall health, however, PA is challenging for many individuals living with chronic pain. Even non-exercise specialists can (cost) effectively promote PA, but many health professionals report a number of barriers in providing guidance on PA, suggesting that it is not consistently promoted. This expert position paper summarizes the evidence and provides five recommendations for health professionals to assess, advise and support individuals living with any chronic pain condition with a long life expectancy in adopting and sustaining physically active lifestyles.

Methods: This position paper was prepared by the 'On The Move' Task Force of the European Pain Federation EFIC. Final recommendations were endorsed by the European Pain Forum, Pain Alliance Europe and the Executive Board of EFIC.

Results: We recommend that all health professionals (1) Take a history of the persons' PA levels, and put PA on the agenda, (2) Advise that PA is important and safe for individuals living with chronic pain, (3) Deliver a brief PA intervention and support individuals living with chronic pain in becoming physically active, (4) Discuss acceptable levels of PA-related soreness and pain and (5) Provide ongoing support in staying physically active.

Significance: Physical activity is safe and offers several advantages, including general health benefits, low risk of side effects, low cost and not requiring access to healthcare. Adoption of these recommendations can improve the quality of care and life of individuals living with chronic pain and reduce their overall health risks.

Abstract
Background: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting.

Methods: We assessed pain 90 days after ambulatory surgery in an international, multicentre prospective cohort study of patients ≥45 years old with comorbidities or ≥65 years old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change ≥1 in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain as a score ≥4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression.

Results: Between November 2021 and January 2023, a total of 2054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain prior to surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were: active smoking (OR 1.82; 95% CI 1.20 to 2.76), orthopaedic surgery (OR 4.7; 95% CI 2.24 to 9.7), plastic surgery (OR 4.3; 95% CI 1.97 to 9.2), breast surgery (OR 2.74; 95% CI 1.29 to 5.8), vascular surgery (OR 2.71; 95% CI 1.09 to 6.7), and ethnicity (i.e., Hispanic/Latino ethnicity OR 3.41; 95% CI 1.68 to 6.9 and First Nations/Native persons OR 4.0; 95% CI 1.05 to 15.4).

Conclusions: Persistent postsurgical pain after same-day surgery is common, usually moderate to severe in nature, and occurs mostly in patients without chronic pain prior to surgery.

Abstract
Shared decision-making (SDM) involving patient and physician is a desirable goal that is recommended in chronic pain management guidelines. This study measured whether SDM affects opioid prescribing frequency for chronic low back pain. A retrospective cohort study involving 1478 participants was conducted within a national pain research registry. The patient participation and patient orientation (PPPO) scale of the Communication Behavior Questionnaire was used to measure SDM, including classification of greater SDM (PPPO scale score≥80) or lesser SDM (PPPO scale score<80). Opioid prescribing frequency was measured at quarterly intervals from enrollment through 12 months. Baseline and longitudinal covariates were collected to adjust for potential confounding using generalized estimating equations. The mean age of participants was 53.1 (SD, 13.2) years and 1098 (74.3%) were female. A total of 473 (32.0%) participants were prescribed opioids at baseline. Participants completed 5968 encounters wherein multivariable analyses demonstrated that PPPO scale scores were associated with more frequent opioid prescribing (β=0.013; 95% CI, 0.005 to 0.021; P<0.001). Greater SDM was associated with more frequent opioid prescribing than lesser SDM (β=0.441; 95% CI, 0.160 to 0.722; P=0.002). Opioids were prescribed in 34.3% vs. 25.2% of encounters with greater vs. lesser SDM (OR, 1.55; 95% CI, 1.17-2.06). SDM remained associated with more frequent opioid prescribing in a series of sensitivity analyses. Although SDM is desirable in chronic pain management, complex issues and challenging patient conversations may arise during serial assessments of the appropriateness of opioid therapy. Physicians need better education and training to address such difficult situations. PERSPECTIVE: The more frequent use of opioid therapy among patients who reported greater shared decision-making with their physicians underscores the need for better medical education and training in dealing with the complex issues and challenges pertaining to serial assessments of the appropriateness of opioid therapy for chronic pain.

Abstract
In this study, we describe the development and validation of a revised Pediatric Chronic Pain Grading (P-CPG) for children aged 8 to 17 years that adds emotional impairment to previously used measures of pain intensity and functional impairment. Such a measure enables the assessment of chronic pain severity in different epidemiological and clinical populations, the stratification of treatment according to pain severity, and the monitoring of treatment outcome. The P-CPG was developed using a representative sample of school children with chronic pain (n = 454; Mage = 12.95, SD = 2.22). Construct validity and sensitivity to change were examined within a sample of N = 2448 children and adolescents (Mage = 12.71, SD = 2.47) comprising 3 subsamples (school n = 1562, primary care n = 129, and tertiary care n = 757) affected by chronic pain to varying extents. Results showed that P-CPG grades differed significantly among the 3 subsamples, with school children being least affected by chronic pain and tertiary care patients being most affected. As P-CPG grade increased, so did pain intensity, functional impairment, pain-related school absence, and emotional impairment. Convergent validity was demonstrated by significant positive correlations between the P-CPG and global ratings of pain severity as well as objective claims data; the latter reflects greater health care costs with increasing P-CPG scores. Sensitivity to change was supported by a significant reduction in baseline P-CPG grades 3 and 6 months after intensive interdisciplinary pain treatment in tertiary care sample. In conclusion, the P-CPG is an appropriate measure of pain severity in children and adolescents with chronic pain in clinical as well as epidemiological settings.

Abstract
Objective: Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months.

Methods: Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded.

Results: Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend.

Conclusion: This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.

Abstract
Background: Persistent postsurgical pain (PPSP) after lung cancer surgery is common and current definitions are based on evaluations at a single time point after surgery. Pain intensity and symptoms may however fluctuate and change over time, and be impacted by multiple and shifting factors. Studies of postoperative recovery patterns and transition from acute to chronic pain are needed for further investigation of preventive measures and treatments to modify unfavourable recovery paths.

Methods: In this explorative study, 85 patients undergoing surgery due to either presumptive or confirmed lung cancer reported pain intensities bi-monthly for 12 months. Pain trajectories during recovery were investigated, using group-based trajectory modelling. Associations with possible risk factors for PPSP, including clinical variables and anxiety and depression score (HADS), were also explored.

Results: A trajectory model containing three 12-month pain recovery groups was computed. One group without PPSP fully recovered (50%) within two to three months. Another group with mild-intensity PPSP followed a protracted recovery trajectory (37%), while incomplete recovery was observed in the last group (13%). Acute postoperative pain and younger age were associated with a less favourable recovery trajectory. More neuropathic pain symptoms were observed in patients with incomplete recovery.

Conclusions: Three clinically relevant recovery trajectories were identified, based on comprehensive pain tracking. Higher acute postoperative pain intensity was associated with an unfavourable pain recovery trajectory.

Significance statement: Understanding the transition from acute to chronic postoperative pain and identifying preoperative risk factors is essential for the development of targeted treatments and the implementation of preventive measures. This study (1) identified distinct recovery trajectories based on frequent pain assessment follow-ups for 12 months after surgery and (2) evaluated risk factors for unfavourable postoperative pain recovery paths. Findings suggest that early higher postoperative pain intensity is associated with an unfavourable long-term recovery path.

Abstract
Background: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology.

Materials and methods: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data.

Results: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed.

Conclusion: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction.

Abstract
Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. Patch-clamp recordings also demonstrated enhanced excitatory synaptic transmission (miniature excitatory postsynaptic currents [EPSCs]) in spinal nociceptive neurons following let-7b perfusion or optogenetic activation of axonal terminals. The elevation in spinal calcium signaling and EPSCs was dependent on the presence of toll-like receptor-7 (TLR7) and transient receptor potential ion channel subtype A1 (TRPA1). In addition, endogenous let-7b is enriched in spinal cord synaptosome, and peripheral inflammation increased let-7b in doral root ganglion/dorsal root ganglia neurons, spinal cord tissue, and the cerebrospinal fluid. Notably, let-7b antagomir inhibited inflammatory pain and inflammation-induced synaptic plasticity (EPSC increase), suggesting an endogenous role of let-7b in regulating pain and synaptic transmission. Furthermore, intrathecal injection of let-7b, at a higher dose (10 μg), induced persistent mechanical allodynia for >2 weeks, which was abolished in Tlr7-/- mice. The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.

Abstract
Chronic overlapping pain conditions (COPCs) by definition frequently co-occur, perhaps reflecting their shared etiologies. Their overlapping nature presents a methodological challenge, possibly masking associations between COPCs and health outcomes attributable to either general or specific processes. To address this challenge, we used population-based cohort data to evaluate the predictive validity of a bifactor model of nine self-reported COPCs by assessing its association with incident pain-related clinical diagnoses; pain-relevant pharmacotherapy; and other health outcomes. We obtained data from a 2005-2006 study of Swedish adult twins linked with health data from nationwide registers through 2016 (N = 25,418). We then fit a bifactor model comprising a general COPC factor and two independent specific factors measuring pain-related somatic symptoms and neck and shoulder pain. Accounting for age, biological sex, and cancer, the general factor was associated with increased risk of all pain-related outcomes (e.g., COPC diagnosis aOR, 1.71; 95% CI [1.62, 1.81]), most mental health-related outcomes (e.g., depression aOR, 1.72 [1.60, 1.85]), and overdose and mortality (e.g., all-cause mortality aOR, 1.25 [1.09, 1.43]). The somatic symptoms specific factor was associated with pain-relevant pharmacotherapy (e.g., prescribed opioids aOR, 1.25 [1.15, 1.36]), most mental health-related outcomes (e.g., depression aOR, 1.95 [1.70, 2.23]), and overdose (e.g., nonfatal overdose aOR, 1.66 [1.31, 2.10]). The neck and shoulder pain specific factor was weakly and inconsistently associated with the outcomes. Findings provide initial support for the validity and utility of a general-factor model of COPCs as a tool to strengthen understandings of co-occurrence, etiology, and consequences of chronic pain. PERSPECTIVE: This article presents associations between a novel measurement model of chronic overlapping pain conditions (COPCs) and various health outcomes. Findings provide support for measuring pain across multiple domains rather than only measuring pain specific to one physical location in both research and clinical contexts.

Abstract
Vulnerability to chronic pain is found to depend on age and sex. Most patients with chronic pain are elderly women, especially with posttraumatic pain after bone fracture that prevails beyond the usual recovery period and develops into a complex regional pain syndrome (CRPS). There, a distal bone fracture seems to initiate a pathophysiological process with unknown mechanism. To investigate whether sex, age, and alpha adrenergic receptors also contribute to a CRPS-like phenotype in animals, we performed experiments on tibia-fractured mice. Those mice commonly are resilient to the development of a CRPS-like phenotype. However, we found them to be vulnerable to long-lasting pain after distal bone fracture when they were of old age. These mice expressed mechanical and thermal hypersensitivity, as well as weight-bearing and autonomic impairment following bone trauma, which persisted over 3 months. Site-specific and body side-specific glycinergic and α1D-noradrenergic receptor expression in the spinal cord and the contralateral locus coeruleus were misbalanced. Aged female tibia-fractured mice lost descending noradrenergic inhibition and displayed enhanced spinal activity on peripheral pressure stimuli. Together, changes in the noradrenergic, hence, glycinergic system towards excitation in the pain pathway-ascending and descending-might contribute to the development or maintenance of long-lasting pain. Conclusively, changes in the noradrenergic system particularly occur in aged female mice after trauma and might contribute to the development of long-lasting pain. Our data support the hypothesis that some patients with chronic pain would benefit from lowering the adrenergic/sympathetic tone or antagonizing α1(D).

Abstract
Objectives: Chronic pain is a significant public health concern. Psychological treatments are effective for treating chronic pain, but long term follow up studies are limited, and treatment effects sizes are small. Identifying modifiable treatment targets, such as emotion regulation, is critical to improve interventions. Emotion regulation (ER; i.e., cognitive and attentional strategies to modulate or maintain emotional experience) has been linked to psychopathology and pain experience in adults. Yet, the existing work is limited and has largely focused on the relationship between emotional experience, not ER, and pain.

Methods: The current study utilized ecological momentary assessment (EMA) to characterize real time, momentary relationships between ER strategies and pain experience (intensity, interference, and negative affect) among 53 (77.4% female; Mage=27.10 y, SD=5.16 y) adults with chronic pain. Participants completed EMA assessments of pain experience and ER strategies five times a day for seven days.

Results: Results of the current study provide evidence for the association between within-person maladaptive ER strategies and pain intensity (b=2.11, se=0.37, P<0.001), pain interference (b=1.25, se=0.40, P=0.002), and pain-related negative affect (b=2.20, se=0.41, P<0.001). Associations by specific strategy type were also examined, highlighting the importance of worry, experiential avoidance, rumination, and expressive suppression in pain experience.

Discussion: Given that emotion regulation is readily targeted in psychological treatments for chronic pain, the results from the current study provide initial evidence to target these ER strategies in treatment.

Abstract
Bodily disruptions have been consistently demonstrated in individuals with chronic low back pain. The performance on the left-right judgment task has been purposed as an indirect measure of the cortical proprioceptive representation of the body. It has been suggested to be dependent on implicit motor imagery, although the available evidence is conflicting. Hence, the aim of this case-control observational study was to examine the performance (accuracy and reaction times) and event-related potentials while performing the left-right judgment task for back and hand images in individuals with chronic low back pain versus healthy controls, along with its relationship with self-reported measurements and quantitative sensory testing. While self-reported data suggested bodily disruptions in the chronic low back pain sample, this was not supported by quantitative sensory testing. Although both groups displayed the same performance, our results suggested an increased attentional load on participants with chronic low back pain to achieve equal performance, measured by a higher N1 peak amplitude in occipital electrodes, especially when the effect of contextual images arises. The absence of differences in the reaction times for the left-right judgment task between both groups, along with inconsistencies in self-reported and quantitative sensory testing data, could question the involvement of implicit motor imagery in solving the task. In conclusion, our results suggest disrupted attentional processing in participants with chronic low back pain to solve the left-right judgment task. PERSPECTIVE: Although there are no differences in the performance of the left-right judgment task (hits, reaction times) between chronic low back pain patients and controls, the analysis of event-related potentials revealed that patients require a higher cognitive load, measured by N1 peak amplitude.

Keywords: back awareness; chronic low back pain; electroencephalography; motor imagery; quantitative sensory testing.

Abstract
To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (EPPIC, ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, BMI, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by 0.74 points (p<0.0001) and GAD-7 by 0.73 points (p<0.0001) on average. Each additional comorbidity/variable was associated with an increase in pandemic PHQ-9 by an average of 0.63 points (p=0.0004) and GAD-7 by 0.53 points (p=0.0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PERSPECTIVE: This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors.

Abstract
Background: Chronic pain is a condition with severe impact on many aspects of life, including work, functional ability and quality of life, thereby reducing physical, mental and social well-being. Despite the high prevalence and burden of chronic pain, it has received disproportionally little attention in research and public policy and the societal costs of chronic pain remain largely unknown. This study aimed to describe the long-term healthcare and work absence costs of individuals with and without self-identified chronic pain.

Methods: The study population were participants in two Norwegian population health studies (HUNT3 and Tromsø6). Participants were defined as having chronic pain based on a self-reported answer to a question on chronic pain in the health studies in 2008. Individuals in the study population were linked to four national register databases on healthcare resource use and work absence.

Results: In our study, 36% (n = 63,782) self-reported to have chronic pain and the average years of age was 56.6. The accumulated difference in costs between those with and without chronic pain from 2010 to 2016 was €55,003 (CI: 54,414-55,592) per individual. Extrapolating this to the entire population suggests that chronic pain imposes a yearly burden of 4% of GDP. Eighty per cent of the costs were estimated to be productivity loss.

Conclusion: Insights from this study can provide a greater understanding of the extent of healthcare use and productivity loss by those with chronic pain and serve as an important basis for improvements in rehabilitation and quality of care, and the education of the public on the burden of chronic pain.

Significance: This was the first study to estimate the economic burden associated with chronic pain in the general population using linked individual-level administrative data and self-reported survey answers. We provide calculations showing that annual costs of chronic pain may be as high as €12 billion or 4% of GDP. Findings from this study highlight the need for a greater understanding of the substantial healthcare use and productivity losses among individuals with chronic pain.

Abstract
Chronic pain and insomnia symptoms are highly comorbid, however the psychological mechanisms driving this comorbidity are not well understood. The aim of the present study was to assess whether two cognitive biases that occur separately in chronic pain and insomnia, i.e. interpretation bias and attentional bias, are heightened in people with comorbid chronic pain and elevated insomnia symptoms. A final sample of N = 109 people with chronic pain and N = 79 people without pain who varied in insomnia symptoms were recruited through Prolific Academic to complete this cross-sectional study. Participants completed measures of sleep and pain-related interpretation bias (ambiguous sentences task) and attentional bias (dot-probe task), as well as questionnaires assessing insomnia symptoms, pain symptoms, and general psychological symptoms. We found an interaction between pain status and insomnia symptoms for sleep-related interpretation bias. That is, people with chronic pain showed greater sleep-related interpretation bias than those without pain, but only when insomnia symptoms were also elevated. This interaction did not extend to pain interpretation bias or attentional bias, although we did find an elevated pain interpretation bias in people with chronic pain compared to pain free individuals. We also found that both pain and sleep-related interpretation bias were associated with depression symptoms, suggesting that interpretation bias could potentially drive a trimorbidity of chronic pain, insomnia and depression. Taken together, these findings suggest promise for the role of interpretation bias in the mutual maintenance of chronic pain and insomnia symptoms, and the importance of also considering depression. PERSPECTIVE: This article presents data on the cognitive biases that are present in chronic pain, and that are associated with increased insomnia symptoms. Identifying such cognitive biases could help in explaining the high comorbidity between chronic pain and insomnia, leading to more effective and targeted treatments.

Abstract
In younger populations, risk factors from psychologically-focused theoretical models have become accepted as primary drivers behind the persistence of low back pain (LBP), but these risk factors have not been thoroughly assessed in older adult populations (60-85 years). To address this knowledge gap, we sought to examine longitudinal associations between both general and pain-related psychological risk factors and future pain intensity, LBP-related disability, and physical function (gait speed) outcomes in older adults with chronic LBP (n=250). Questionnaires for general (i.e., depressive symptoms) and pain-related psychological risk factors (i.e., fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were collected at baseline. Questionnaire values were entered into principal component analysis to yield a combined psychological component score. LBP intensity (pain thermometers), LBP-related disability (Quebec Back Pain Disability Scale [QBPDS)]), and gait speed were measured at baseline and 12-month follow-up. Multiple linear regression was used to examine adjusted associations between baseline psychological component scores and each prospective outcome. The baseline psychological component score failed to independently predict 12-month LBP-related disability and gait speed after adjustment for baseline outcomes. Though the psychological component score was associated with 12-month LBP intensity after adjusting for baseline LBP intensity, this association diminished with full adjustment for other baseline characteristics. Cumulatively, general and pain-related psychological risk factors did not independently predict longitudinal pain, disability, and physical function outcomes in this cohort. Compared to younger populations with this condition, general and pain-related psychological risk factors may have less influence on the maintenance of chronic LBP in older adults. PERSPECTIVE: This article failed to establish consistent independent relationships between psychological factors and worse longitudinal pain, disability, and physical function outcomes in older adults with chronic LBP. The findings highlight a need to determine other age-specific biopsychosocial risk factors that may impact the maintenance of chronic pain in this patient population.

Abstract
Objectives: Our purpose was to explore the effect of remifentanil on acute and chronic postsurgical pain after cardiac surgery.

Methods: Randomized controlled trials (RCTs) were retrieved in electronic databases such as PubMed, Cochrane Library, CNKI databases, Scopus, and Web of Science. A systematic review, meta-analysis, trial sequential analysis (TSA) was performed. Basic information and outcomes were extracted from the included studies. The primary outcome was chronic postsurgical pain. Secondary outcomes were scores of postsurgical pain and morphine consumption within 24 hours after cardiac surgery. Our risk of bias assessment was based on the Cochrane risk of bias tool version 2 (ROB 2.0). The overall quality of the evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results: Seven studies consisting of 658 patients were enrolled in the meta-analysis. A single study had a high risk of bias and two studies had a moderate risk of bias. The incidence of chronic postsurgical pain (four studies [415 patients]; RR, 1.02 [95% CI, 0.53-1.95]; P =0.95; I2=59%; TSA-adjusted CI, 0.78-1.20) and the postsurgical pain score (two studies [196 patients]; MD 0.09 [95% CI, -0.36-0.55]; P =0.69; I2=0%; TSA-adjusted CI, -0.36-0.55）were not statistically different between the two groups. However, morphine consumption (six studies [569 patients]; MD 6.94 [95% CI, 3.65-10.22]; P<0.01; I2=0%; TSA-adjusted CI, 0.00-0.49) was higher in the remifentanil group than in the control group.

Discussion: There was not enough evidence to prove that remifentanil can increase the incidence of chronic postsurgical pain after cardiac surgery, but interestingly, the results tended to support a trend toward increased complications in the intervention group. However, there was moderate-certainty evidence that the use of remifentanil increases the consumption of morphine for analgesia, and more direct comparison trials are needed to inform clinical decision-making with greater confidence.

Abstract
Chronic painful knee osteoarthritis (OA) is a disabling physical health condition. Alterations in brain responses to arthritic changes in the knee may explain persistent pain. This study investigated source localised, resting-state electroencephalography (rsEEG) activity and functional connectivity in people with knee OA, compared to healthy controls (HC). Adults aged 44-85 years with knee OA (n=37) and HC (n=39) were recruited. rsEEG was collected for 10 minutes and decomposed into infraslow frequency (ISF) to gamma frequency bands. Standard low-resolution electromagnetic brain tomography (sLORETA) statistical non-parametric maps were conducted, current densities of regions of interest were compared between groups and correlation analyses were performed between EEG measures and clinical pain and functional outcomes in the knee OA group. sLORETA non-parametric maps revealed higher (p=0.006) gamma band activity over the right insula (RIns) in the knee OA group. A significant (p<0.0001) reduction in ISF band activity at the pregenual anterior cingulate cortex (pgACC), whereas higher theta, alpha, beta, and gamma band activity at the dorsal anterior cingulate cortex (dACC), pgACC, the somatosensory cortex (SSC), and RIns in the knee OA group were identified. ISF activity of dACC was positively correlated with pain measures and psychological distress scores. Theta and alpha activity of RIns were negatively correlated with pain interference. In conclusion, aberrations in infraslow and faster frequency EEG oscillations at sensory-discriminative, motivational-affective, and descending inhibitory cortical regions were demonstrated in people with chronic painful knee OA. Moreover, EEG oscillations were correlated with pain and functional outcome measures. PERSPECTIVE: This study confirms alterations in the rsEEG oscillations and its relationship with pain experience in people with knee OA. The study provides potential cortical targets and the EEG frequency bands for neuromodulatory interventions for managing chronic pain experience in knee OA.

Abstract
Despite the crucial role of effective and sustained extinction of conditioned pain-related fear in cognitive-behavioral treatment approaches for chronic pain, experimental research on extinction memory retrieval in chronic pain remains scarce. In healthy populations extinction efficacy of fear memory is affected by stress. Therefore, we investigated the effects of oral hydrocortisone administration on the the reinstatement of pain-related associations in 57 patients with chronic back pain (CBP) and 59 healthy control (HC) participants in a differential pain-related conditioning paradigm within a placebo-controlled, randomized and double-blind design. Participants' skin conductance responses indicate hydrocortisone-induced reinstatement effects in HCs but no observable reinstatement in HCs receiving placebo treatment. Interestingly, these effects were reversed in patients with CBP, i.e., reinstatement responses were only observed in the placebo and not in the hydrocortisone group. Our findings corroborate previous evidence of stress-induced effects on extinction efficacy and reinstatement of fear memory in HCs extending them into the pain context and call for more research to clarify the role of stress in fear extinction and return of fear phenomena possibly contributing to treatment failure in chronic pain treatment. PERSPECTIVE: Opposing effects in HCs and patients with CBP may be associated with changes in the patients' stress systems. These findings could be of relevance to optimize psychological, extinction-based treatment approaches.

Abstract
Purpose: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline.

Methods: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence.

Results: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low.

Conclusion: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty.

Abstract
Background: Among the adaptations of movement consistently associated with disability in chronic pain, guarding is common. Based on previous work, we sought to understand better the constituents of guarding; we also used the concept of flow to explore the description of un/naturalness that emerged from physiotherapists' descriptions of movement in chronic pain. The aim was to inform the design of technical systems to support people with chronic pain in everyday activities.

Methods: Sixteen physiotherapists, experts in chronic pain, were interviewed while repeatedly watching short video clips of people with chronic low back pain doing simple movements; physiotherapists described the movements, particularly in relation to guarding and flow. The transcribed interviews were analysed thematically to elaborate these constructs.

Results: Moderate agreement emerged on the extent of guarding in the videos, with good agreement that guarding conveyed caution about movement, distinct from biomechanical variables of stiffness or slow speed. Physiotherapists' comments on flow showed slightly better agreement, and described the overall movement in terms of restriction (where there was no flow or only some flow), of tempo of the entire movement, and as naturalness (distinguished from normality of movement).

Conclusions: These qualities of movement may be useful in designing technical systems to support self-management of chronic pain.

Significance: Drawing on the descriptions of movements of people with chronic low back pain provided by expert physiotherapists to standard stimuli, two key concepts were elaborated. Guarding was distinguished from stiffness (a physical limitation) or slowness as motivated by fear or worry about movement. Flow served to describe harmonious and continuous movement, even when adapted around restrictions of pain. Movement behaviours associated with pain are better understood in terms of their particular function than aggregated without reference to function.

Abstract
Persistent pain is a major public health issue - estimated to affect a quarter of the world's population. Public understanding of persistent pain is based on outdated biomedical models, laden with misconceptions that are contrary to best evidence. This understanding is a barrier to effective pain management. Thus, there have been calls for public health-based interventions to address these misconceptions. Previous pain focussed public education campaigns have targeted pain beliefs and behaviours that are thought to promote recovery, such as staying active. However, prevailing pain-related misconceptions render many of these approaches counter-intuitive, at best. Pain Science Education improves understanding of 'how pain works' and has been demonstrated to improve pain and disability outcomes. Extending Pain Science Education beyond the clinic to the wider community seems warranted. Learning from previous back pain-focussed and other public health educational campaigns could optimise the potential benefit of such a Pain Science Education campaign. Pain Science Education-grounded campaigns have been delivered in Australia and the UK and show promise, but robust evaluations are needed before any firm conclusions on their population impact can be made. Several challenges exist going forward. Not least is the need to ensure all stakeholders are involved in the development and implementation of Pain Science Education public messaging campaigns. Furthermore, it is crucial that campaigns are undertaken through a health equity lens, incorporating underrepresented communities to ensure that any intervention does not widen existing health inequalities associated with persistent pain. PERSPECTIVE: Public misconceptions about pain are a significant public health challenge and a viable intervention target to reduce the personal, social, and economic burden of persistent pain. Adaptation of Pain Science Education, which improves misconceptions in a clinical setting, into the public health setting seems a promising approach to explore.

Abstract
Objectives: Patients' beliefs about pain play an important role in their readiness to engage with chronic pain self-management. The central aim of this study was to validate a self-report instrument to assess a specific set of pain beliefs, patients' endorsement of a biopsychosocial model of chronic pain (PEB).

Methods: Interdisciplinary experts in the field of pain were involved in creating an instrument, the PEB Scale, to operationalize patients' endorsement of a biopsychosocial model. A sample of 199 patients with chronic pain was recruited to evaluate the factorial structure (principal axis factoring), the internal consistency (Cronbach's alpha), the convergent and discriminant validity (correlational analyses), incremental validity (multiple, hierarchical regression analyses), and construct validity (differential population analysis) of the instrument.

Results: The factor analysis resulted in a unidimensional, 11-item instrument that explained 51.2% of the total variance. Cronbach's alpha (= 0.92) indicated high internal consistency of the created set of pain-related beliefs. Regression analyses demonstrated that PEB is a strong predictor of patients' engagement with pain self-management (P < 0.001), after controlling for demographic variables, anxiety, depression, and other pain-related beliefs.

Discussion: Our results show that the PEB Scale is a highly reliable self-report instrument, which has the potential to predict patients' readiness to adopt pain self-management. Future research should focus on re-validating the scale we developed to operationalize PEB. Moreover, the PEB Scale should be implemented in longitudinal study designs to investigate its ability to predict the transition from acute to chronic pain and patients' long-term pain management.

Abstract
A variety of evidence-based psychosocial treatments now exist for chronic pain. However, on average, effect sizes have tended to be modest and there is a high degree of heterogeneity in treatment response. In this focus article, we explore the potential role that therapist quality in delivering treatment may have in accounting for a degree of this variability in outcome. Therapist quality refers to the skillful delivery of treatment, harnessing both specific and common therapeutic factors during sessions. While recognized as important to assess and report in clinical trials by some reporting guidelines, few randomized controlled trials evaluating psychosocial treatments for chronic pain have reported on therapist factors. We reviewed the clinical trials included in three systematic reviews and meta-analyses of trials of cognitive-behavioral therapy (mainly), mindfulness-based interventions and acceptance and commitment therapy. We found that of the 134 trials included, only nine assessed and reported therapist quality indicators, with a variety of procedures used. This is concerning as without knowledge of the quality in which treatments are delivered, the estimates of effect sizes reported may be misrepresented. We contextualize this finding by drawing on the broader psychotherapy literature which has shown that more skillful, effective therapists demonstrated ten times better patient response rates. Examination of the characteristics associated with these more effective therapists tends to indicate that skillful engagement of common factors in therapy sessions represents a distinguishing feature. We conclude by providing recommendations for assessing and reporting on therapist quality within clinical trials evaluating psychosocial treatments for chronic pain. PERSPECTIVE: Therapist quality in the delivery of psychosocial treatments for chronic pain has rarely been assessed in clinical trials. We propose that therapist quality indicators are an under-studied mechanism which potentially contribute to the heterogeneity of treatment outcomes. We provide recommendations for assessing and reporting on therapist quality in future trials.

Abstract
Background: Chronic pain is a recognized complication of surgery, and it has been hypothesized that regional anesthesia might reduce the risk of development of chronic pain after upper extremity surgery.

Methods: A systematic literature review was performed to assess whether in patients undergoing elective upper extremity surgery (P), regional anesthesia (I), compared to general anesthesia (C), would result in lower long-term (>3 months) postoperative pain intensity (O). We included randomized and nonrandomized controlled trials (RCTs). Our primary outcome was numerical rating score or visual analogue scale for pain, at >3 months postoperatively. The Embase, Medline ALL, Web of Science Core Collections, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for all reports assessing pain at >3 months after upper extremity surgery under general versus regional anesthesia. Secondary outcomes were: opioid prescription filling, complex regional pain syndrome (CRPS) incidence, the Mayo Wrist Score (MWS), and scores on the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Quality (or certainty) of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Risk-of-bias was assessed using the Cochrane tool for randomized trials (RoB 2.0) and nonrandomized trials (ROBINS-I).

Results: This review included 14 studies, comprising 7 RCTs and 7 nonrandomized studies. Six of the 7 studies (4 RCTs, N = 273; 2 nonrandomized studies, N = 305) using a pain score, our primary outcome, report comparable long-term postoperative pain scores after regional and general anesthesia. Six of the 7 studies using our secondary outcomes report comparable long-term outcomes in terms of opioid prescription filling (2 retrospective cohort studies [RCSs], N = 89,256), CRPS incidence (1 RCT, N = 301), MWS (1 RCT and 1 RCS, N = 215), and DASH score (1 RCT, N = 36). Comparable outcomes were reported in all 7 RCTs (N = 778) and in 5 of the 7 nonrandomized studies, comprising 5 RCSs (N = 89,608). Two prospective observational studies (POSTs), comprising 279 patients, report a statistically significant difference in outcomes, with less pain and better DASH scores after brachial plexus anesthesia. All 14 studies provided moderate to very low certainty evidence, and there was a serious risk of bias due to confounding bias in 5 of the 7 nonrandomized studies (N = 631).

Conclusions: The results of this review indicate that upper extremity regional anesthesia, compared to general anesthesia, is unlikely to change pain intensity at >3 months postoperatively.

Abstract
Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Abstract
A growing body of literature describes the use of buprenorphine for the treatment of chronic pain in people with sickle cell disease. The experiences of people with sickle cell disease who have tried buprenorphine are not yet reported. This qualitative descriptive study was conducted to explore perspectives on buprenorphine for chronic pain in sickle cell disease. We interviewed 13 participants with sickle cell disease who had been prescribed buprenorphine and had a clinic visit between December 1, 2020 and April, 2022 in our Sickle Cell Center for Adults. Interviews were recorded, transcribed, and analyzed using thematic analysis. Eleven out of 13 participants were taking buprenorphine at the time of the interview, with mean treatment duration of 33 months (SD 18, range 7 to 78 months). Five major themes were identified: 1) dissatisfaction with full agonist opioids; 2) navigating uncertainty with autonomy in deciding to try buprenorphine; 3) functional and relational changes after starting buprenorphine, 4) enduring systemic barriers to pain treatment, and 5) trusting treatment relationships are necessary when approaching patients about buprenorphine. The experience of adulthood living with sickle cell disease before and after starting buprenorphine is qualitatively different with significant improvements in social functioning. PERSPECTIVE: This study examined the experience of adults with sickle cell disease and chronic pain transitioning from full agonist opioids to buprenorphine. It is the first qualitative study of buprenorphine in people with sickle cell disease, contributing to a small but growing literature about buprenorphine and sickle cell disease.

Abstract
The ATP-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. Then, we analyzed these variants for statistical association with chronic pain phenotypes using both individual P2RX7 variants as predictors and cumulative allele counts of same-direction cellular effect in univariate models. Association and validation analyses were conducted in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort (N=3260) and in the Complex Persistent Pain Conditions (CPPC) cohort (N= 900), respectively. Our results showed an association between allele A of rs7958311 and an increased risk of chronic pelvic pain, with convergent evidence for contribution to fibromyalgia and irritable bowel syndrome (IBS), confirmed in meta-analysis. This allelic variant produced a unique cellular phenotype: a gain-of-function (GOF) in channel opening, and loss-of-function (LOF) in pore opening. Computational study using a 12-state Markov model of ATP binding to the P2X7 receptor suggested that this cellular phenotype arises from an increased ATP binding affinity and an increased open channel conductance combined with a loss of sensitization. Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of GOF in channel and LOF in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PERSPECTIVE: This study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.

Abstract
Inflammation is linked with chronic pain but the extent to which this relationship is associated with biopsychosocial factors is not known. We investigated relationships between blood C-reactive protein (CRP) and regional chronic pain conditions adjusting for a large range and number of potential confounders. We performed cross-sectional analyses using the UK Biobank (N=415,567) comparing CRP in people reporting any of nine types of regional chronic pain with pain-free controls. Using logistic regression modelling, we explored relationships between CRP and the presence of chronic pain, with demographic, socioeconomic, psychological/lifestyle factors, and medical comorbidities as covariates. CRP was higher in chronic pain at any site compared with controls (Females: median [IQR] 1.60mg/L [2.74] vs 1.17mg/L [1.87], P<0.001; Males: 1.44mg/L [2.12] vs 1.15mg/L [1.65], P<0.001). In males, associations between CRP and all types of chronic pain were attenuated but remained significant after adjustment for biopsychosocial covariates (OR range 1.08 to 1.49, P≤0.001). For females, adjusted associations between CRP and pain remained significant for most chronic pain types (OR range 1.07 to 1.34, P<0.001) except for facial pain (OR 1.04, P=0.17) and headache (OR 1.02, P=0.07)-although these non-significant findings may reflect reduced sample size. The significant association between CRP and chronic pain after adjustment for key biopsychosocial confounders implicates an independent underlying biological mechanism of inflammation in chronic pain. The presence of yet unknown or unmeasured confounding factors cannot be ruled out. Our findings may inform better targeted treatments for chronic pain. PERSPECTIVE: Using a large-scale dataset, this article investigates associations between chronic pain conditions and blood C-reactive protein (CRP), to evaluate the confounding effects of a range of biopsychosocial factors. CRP levels were higher in those with chronic pain vs controls after adjusting for confounders-suggesting a possible independent biological mechanism.

Abstract
Background: Chronic pain is the hallmark symptom of joint diseases. This study examined the differences in quantitative sensory testing between patients with psoriatic arthritis (PsA), hand osteoarthritis (hand-OA) and a pain-free control group and differences between patients with and without concomitant fibromyalgia (cFM).

Methods: All patients and pain-free controls were assessed using pressure pain thresholds (PPT), temporal summation of pain (TSP), conditioned pain modulation (CPM) and clinical pain intensities. Psychological distress was assessed with the Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Pittsburgh Sleep Quality Index. Disability was assessed with the Health Assessment Questionnaire and pain quality with the painDETECT questionnaire. cFM was identified using the revised 2016 American College of Rheumatology diagnostic criteria.

Results: Patients with hand-OA (n = 75) or PsA (n = 58) had statistically significant lower PPTs and CPM, greater TSP, and higher scores of psychological distress (p < 0.05) than controls (n = 20). Patients with cFM (58%) had higher scores of depression (p = 0.001), anxiety (p = 0.004), catastrophizing (p = 0.012), disability (p < 0.001), higher painDETECT score (p = 0.001), TSP (p = 0.027), and reduced sleep quality (p = 0.021) when compared to patients without cFM.

Conclusion: Patients with hand-OA and PsA exhibited signs of pain sensitization and a higher degree of psychological distress and disability than pain-free individuals. Patients with cFM had greater TSP, painDETECT score, disability, catastrophizing, and reduced sleep quality, than patients without, indicating greater degree of pain sensitization, psychological burden, and disability.

Statement of significance: This paper shows that a significant proportion of patients with hand osteoarthritis and psoriatic arthritis with moderate pain intensity have significantly increased signs of pain sensitization and markers of psychological distress. A large proportion of these patients fulfil the criteria for concomitant fibromyalgia and these patients show even greater propensity towards pain sensitization and psychological distress.

Abstract
Background and objective: A network analysis can be used to quantitatively assess and graphically describe multiple interactions. This study applied network analyses to determine the interaction between physical and pain-related factors and fear of movement in people with whiplash-associated disorders (WAD) during periods of acute and chronic pain.

Methods: Physical measurements, including pressure pain-thresholds (PPT) over neural structures, cervical range of motion, neck flexor and extensor endurance and the cranio-cervical flexion test (CCFT), in addition to subjective reports including the Tampa Scale of Kinesiophobia (TSK-11), Neck Disability Index (NDI) and neck pain and headache intensity, were assessed at baseline in 47 participants with acute WAD. TSK-11, NDI and pain intensity were assessed for the same participants 6 months later (n = 45). Two network analyses were conducted to estimate the associations between features at baseline and at 6 months and their centrality indices.

Results: Both network analyses revealed that the greatest weight indices were found for NDI and CCFT at baseline and for neck pain and headache intensity and NDI and TSK-11 at both time points. Associations were also found betweeen cervical muscle endurance and neck pain intensity in the acute phase. Cervical muscle endurance assesssed during the acute phase was also associated with NDI after 6 months - whereas PPT measured at baseline was associsated with headache intensity after 6 months.

Conclusion: The strongest associations were found for headache and neck pain intensity and neck disability and fear of movement, both during acute pain and when mesured 6 months later. The extent of neck endurance and measures of PPT at baseline may be associated with neck disability and headache, respectively, 6 months after a whiplash injury.

Significance: Through two network analyses, we evaluated the interaction between pain-related factors, fear of movement, neck disability and physical factors in people who had experienced a whiplash injury. We demonstrated that physical factors may be involved in the maintenance and development of chronic pain after a whiplash injury. Nevertheless, the strongest associations were found for headache and neck pain intensity and neck disability and fear of movement, both during acute and chronic phases.

Abstract
Objectives: The Patient-Specific Functional Scale (PSFS) has been used to assess physical functioning in various chronic pain populations. There is a lack evidence for its use with diverse pain populations who have high impact chronic pain (HICP). The primary aim of this study was to assess the psychometric properties of the PSFS with a heterogeneous sample of patients with HICP.

Methods: A retrospective observational study of prospective functional outcomes collected before and after participation an intensive pain management program (IPMP): (PSFS, Disabilities of the Arm, Shoulder, and Hand; Lower Extremity Functional Scale; Neck Disability Index; Oswestry Disability Index), Multidimensional Patient Impression of Change, pain intensity, pain limitation, and fear avoidance from the charts of 509 IPMP completers. The reliability, validity, and responsiveness of the PSFS were analyzed using Cronbach's alpha, Pearson correlations, and receiver operating characteristic.

Results: Significant improvements were found for all outcomes following program participation (all p's <0.0001). Correlations of the PSFS with similar outcomes (convergent validity) were lower than expected (r's 0.16 - 0.33). A low correlation (r=-0.12) with an unrelated measure, fear-avoidance, supported divergent validity. PSFS change score correlations with similar outcome measures ranged from 0.46 to 0.53. The area under the curve values for the PSFS ranged from 0.801 to 0.857 suggesting a moderate ability for the PSFS to detect improvement.

Discussion: The psychometric properties of the PSFS showed mixed support for construct validity but good support for the responsiveness of the PSFS when used with a heterogeneous sample of patients with HICP.

Abstract
Objectives: Chronic pain is a significant health concern that adversely affects all aspects of life, including emotional well-being. Opioids are prescribed for the management of refractory, severe chronic pain although they have been associated with adverse effects, including addiction and overdose. The aim of this study was to examine factors that predict thoughts of self-harm among adults with chronic pain who are prescribed opioids.

Methods: Seven hundred sixty-five (N=765) persons with opioid-treated chronic lower back pain completed the Current Opioid Misuse Measure (COMM) and other validated questionnaires as part of a larger study. Response to one question from the COMM ("How often have you seriously thought about hurting yourself?") was used to assess suicide risk on a 5-point scale (0=Never; 4=Very Often).

Results: Participants were categorized into 3 groups according to their responses on the self-harm question: Never (N=628; 82.1%), Seldom or Sometimes (N=74; 9.7%) and Often or Very Often (N=63; 8.2%). Multivariate adjusted odds ratio (aOR) analyses indicated that reports of alcohol or drug overuse within the past month (aOR=1.41,[95% conf interval 1.11-1.78]), post-traumatic stress (PTSD; aOR=1.24,[1.07-1.44]), pain catastrophizing (aOR=1.03,[1.01-1.05]), not loving oneself (aOR=0.99,[.98-1.00]) and poor perceived mental health (aOR=0.94,[.92-.97]) were most associated with thoughts of self-harm. Importantly, ideation frequency of self-harm was highest among individuals treated with higher daily doses of opioids.

Discussion: These results support the need for continued monitoring of adults treated with opioids for chronic pain, particularly among those on high-dose opioids who present with increased negative affect and concerns of substance misuse.

Abstract
Cross-national research using data from the Health Behavior in School-aged Children (HBSC) survey showed an increase in the prevalence of chronic back pain from 2002 to 2014. However, it is unknown if this trend has persisted beyond 2014. The aims of this study were to: (1) determine if the prevalence of chronic back pain in girls and boys aged 11, 13, and 15 continued to increase from 2014 to 2018; and if this was the case, to (2) examine whether this increase in the prevalence of chronic back pain between 2002 and 2018 was explained indirectly by increases in sleep difficulties and in psychological symptoms. Data from 789,596 adolescents retrieved from five waves of the HBSC survey conducted in 2002, 2006, 2010, 2014, and 2018 in 32 countries/regions were used. Logistic regressions and path analyses were conducted. Results showed an overall increase of 0.5% in the prevalence of chronic back pain between 2014 and 2018, ranging from 0.4% for 15-year-old girls to 1.3% for 11-year-old boys, indicating a continued overall increase in chronic back pain in adolescents beyond 2014. For 13-year-old girls and for 15-year-old girls and boys, the increase in the prevalence of chronic back pain between 2002 and 2018 was partially mediated by increases in sleep difficulties which in turn were associated with increases in psychological symptoms. The findings provide important information that may aid stakeholders enhancing public health initiatives to prevent or reduce the increasing trend in the prevalence of chronic back pain in adolescents. PERSPECTIVE: This study shows that chronic back pain prevalence continues to increase among adolescents, with sleep difficulties and psychological symptoms contributing significantly to this trend. The findings provide insights that may inform strategies to prevent or reduce the increasing trend of chronic back pain in adolescents.

Abstract
Background: Chronic neck pain (CNP) is a common musculoskeletal disorder. Pain neuroscience education (PNE) is a promising nonpharmacological intervention for CNP, however, its effectiveness remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness of PNE in treating CNP.

Methods: Electronic databases from inception to February 2023 were searched for randomized controlled trials (RCTs) on the effects of PNE on CNP. The primary outcome was the change in pain intensity, and the secondary outcome was improvement in kinesiophobia, standardized using Hedges' g. Two authors independently scrutinized eligible articles, extracted data and assessed quality; a random-effects model was employed for data pooling.

Results: In total, seven RCTs comprising 479 participants were included and demonstrated that PNE significantly reduced pain intensity (Hedges' g = -0.730, 95% CI = -1.340 to -0.119, p = 0.019, I2 = 89.288%). Subgroup analysis revealed that the adult group experienced significant pain reduction after PNE, whereas the adolescent group did not. PNE also reduced kinesiophobia which was evaluated in four of seven RCTs (Hedges' g = -0.444, 95% CI = -0.735 to -0.154, p = 0.003, I2 = 36.822%). The meta-regression analysis indicated that an increased intervention duration contributed to greater pain reduction. No adverse events were reported following PNE or the control treatment.

Conclusions: PNE effectively reduced pain intensity and kinesiophobia in patients with CNP. A longer PNE time leads to greater pain reduction and is more effective in adults than in adolescents. Further studies are required to examine the long-term effects on CNP management.

Significance: This is the first meta-analysis evaluating the effectiveness of treating chronic neck pain with pain neuroscience education. Pain neuroscience education is successful in reducing pain and decreasing kinesiophobia in the chronic neck pain population. Longer treatment time leads to greater pain reduction.

Abstract
Background: Pain in chronic heart failure (HF) is a significant but often unrecognized symptom. Characteristics of pain in subjects with HF are largely undescribed. The study aimed to address a knowledge gap in the relationship between HF and pain by investigating the prevalence of chronic pain and chronic widespread pain (CWP) among subjects with HF.

Methods: Population data from the HUNT3 study in Norway (2006-2008, n = 50,802) was used. HF was measured by self-report. CWP was defined as having pain in both sides of the body, pain in the upper and lower limbs, and axial pain for at least 3 months in the last year. Associations between HF and CWP and HF and moderate to high pain intensity were analysed with logistic regression.

Results: Among subjects with HF in the general population, the prevalence of chronic pain was 67.8%, 20.7% had CWP, and 58.8% had moderate to high intensity pain. Compared to participants with cardiovascular disease but not HF, the odds of both CWP (OR = 1.6; 95% CI: 1.3-2.0) and moderate to high intensity pain (OR = 1.3; 95% CI: 1.3-1.8) were higher among participants with HF-controlled for age, sex, body mass index, and comorbidity.

Conclusions: Our study confirmed the high prevalence of pain among HF subjects. This pain could not be explained by comorbidity or sociodemographic factors, which are relevant for clinical and research purposes. Pain management should not be restricted to cardiac-related pain but to chronic pain in general.

Significance: This epidemiological study corroborates previous studies reporting a high prevalence of pain in the HF-population. We found that the relationship between HF, CWP, and pain intensity could not be explained by comorbidity or sociodemographic factors, illustrating the burden of chronic pain related to HF. Our results expand the understanding of pain in HF and highlight the need to identify and manage chronic pain among individuals with HF, as widespread pain adds to the symptom burden in individuals with HF.

Abstract
Lateral epicondylalgia, commonly referred to as tennis elbow, is a musculoskeletal condition characterised by pain and sensorimotor dysfunction. In some individuals with chronic unilateral LE, sensorimotor symptoms develop on the unaffected side despite no evidence of tissue damage. Altered interhemispheric inhibition (IHI) is one mechanism that could underpin this phenomenon. The aim of this cross-sectional study was to examine IHI between the primary motor cortices (M1) in individuals with chronic LE and healthy controls. In 20 individuals with chronic LE and 20 healthy participants, transcranial magnetic stimulation was used to assess i) short and long latency IHI from the affected (corresponding to the injured side) to the unaffected M1, and ii) corticomotor excitability of the affected and unaffected M1. Sensorimotor function was evaluated bilaterally at the extensor carpi radialis brevis muscle using pressure pain threshold, grip strength, two-point discrimination and temporal summation tests. Short- and long-latency IHI from the affected to the unaffected M1, and corticomotor excitability of the affected and unaffected M1, were not altered in individuals with LE compared with healthy participants. No differences in sensorimotor function were observed for the affected or unaffected ECRB muscles when individuals with LE were compared with healthy participants. IHI is not altered in individuals with chronic LE. Further studies are required to determine the mechanisms that underpin the development of bilateral sensorimotor symptoms in unilateral LE. PERSPECTIVE: IHI is unaltered from the affected M1 (corresponding to the painful muscle) to unaffected M1 in individuals with LE compared to healthy controls. The absence of bilateral sensorimotor dysfunction and low pain severity in this cohort of individuals with LE may explain this finding.

Abstract
Non-specific chronic low back pain (nCLBP) has been associated with nutrition. Yet, it is not clear how nutritional factors and nCLBP relate to one another. Therefore, the aim of the present study was to investigate differences in diet quality and dietary intake levels between nCLBP patients and healthy controls (HCs) and to explore the association between nutritional factors and pain sensitivity in nCLBP. In this case-control study, 106 participants (i.e., n=53 nCLBP and n=53 HCs) were recruited and completed a 3-day food diary to assess their dietary intake, which allowed to generate individual diet quality scores, (i.e., the healthy eating index-2015 and dietary inflammatory index). Additionally, each participant underwent an experimental pain assessment (quantitative sensory testing) and filled out self-reported pain questionnaires. Compared to HCs, the nCLBP group showed significantly lower diet quality, higher inflammatory scores, and a lower intake of total protein, total fat, dietary fibre, omega-3 fatty acids, vitamin B6, vitamin A, beta-carotene, vitamin E, and magnesium. Pain sensitivity mainly showed a negative correlation with nutritional intakes known for anti-inflammatory properties (i.e., vitamins E, D, A, B6, B12, and zinc). Interestingly, total fat, cholesterol, saturated, and monounsaturated fat intakes were found to be inversely associated with pain sensitivity. Overall, patients with nCLBP have a lower diet quality, eat more pro-inflammatory, have less intake of nutrients known for their anti-inflammatory and anti-oxidative properties, and drink less water compared to HCs. Accordingly, pain sensitivity was mainly found to be positively associated with pro-inflammatory dietary intake. PERSPECTIVE: This study emphasizes the association between a pro-inflammatory diet and non-specific chronic low back pain (nCLBP). Among nCLBP patients, positive association between increased pain sensitivity and the pro-inflammatory potential of a diet, highlighting the potential for individualized pain management strategies and leading to the development of novel therapeutic methods.

Abstract
Despite known health disparities in chronic pain conditions between rural and urban adults, few studies have examined whether longitudinal associations among psychological stress and hand pain differ between them. Utilizing community-based cohort data, this study examined whether rural and urban adults differed in the extent to which psychological distress was associated with hand osteoarthritis (OA) symptoms and later functional limitations related to hand pain. Community dwelling adults (mean age = 51.97, 52.3% women) in a rural (n = 2971) and urban area (n = 2782) provided demographic data at baseline and, at a 4-year follow-up, responded to questionnaires about psychological distress and clinical symptoms of hand OA. Levels of functional limitations in hands were assessed at a 8-year follow-up. Ordinal logistic and linear regression was conducted to examine the effects of psychological distress on hand OA symptoms and functional limitations, and whether associations between psychological distress and these pain outcomes were moderated by residential area. The results showed that psychological distress was associated with higher risk for hand OA symptoms and functional limitations, even after adjusting for demographic and health covariates. There was significant moderation by residential area, such that the association between psychological distress and hand OA was significant only among rural adults and the association with functional limitations was stronger in rural adults than urban adults. Findings suggest greater vulnerability to hand arthritis and hand related functional limitations among rural adults and the potential for tailored intervention programs to help resolve health disparities among rural communities. PERSPECTIVE: This study compares the association between psychological distress and hand pain outcomes between rural and urban adults using community-based cohort data and suggests that rural adults are more vulnerable to experience negative effects of psychological distress on concurrent hand osteoarthritis symptoms and longitudinal functional limitations in hands.

Abstract
Insomnia has been identified as a predictor of reduced benefit from cognitive-behavioral treatment (CBT) for adolescent chronic pain; however, it is not well understood how insomnia leads to reduced treatment response. The purpose of this study was to evaluate executive function and self-management processes as two potential mediators of the relationship between insomnia symptoms and pain-related disability outcomes from internet-delivered CBT using a single-arm clinical trial design. Eighty-five adolescents with chronic pain (77% female, ages 12-17 years) and their caregiver received an eight-week internet-delivered CBT intervention. Youth completed validated measures of insomnia symptoms, executive function, self-management processes, and pain-related disability at baseline, mid-treatment, immediate post-treatment, and three-month follow-up. Results from multilevel structural equation modeling indicated that more severe insomnia symptoms were associated with greater problems with executive function which, in turn, lead to lower engagement in self-management processes and less improvement in pain-related disability. These findings identify two mediators by which higher insomnia symptoms may lead to reduced benefit from CBT intervention for chronic pain. Research is needed to understand whether psychological treatments for chronic pain may be optimized by strategies targeting insomnia, executive function, and/or engagement in self-management. This trial was registered at clinicaltrials.gov (NCT04043962). PERSPECTIVE: Our study suggests that executive functioning and self-management processes mediate the relationship between insomnia and treatment outcomes for pediatric chronic pain, highlighting the impact of insomnia on youth learning and implementation of self-management strategies and the critical need for targeted sleep interventions in this population.

Abstract
Ten chronic overlapping pain conditions are currently recognized by the National Institutes of Health Pain Consortium (e.g., irritable bowel syndrome, chronic migraine headache, and chronic low back pain). These conditions affect millions of Americans, however, assessing these conditions, their co-occurrence, and their relationship to treatment has proven challenging due to time-constraints and a lack of standardized measures. We present a Chronic Overlapping Pain Conditions Screener that is logic-driven, efficient, and freely available in electronic format to non-profit entities. Thirty experts were convened to identify and modify self-report criteria for each Chronic Overlapping Pain Condition as well as criteria that trigger the administration of the diagnostic criteria from a body map and brief series of questions. Their recommendations were then programmed into Research Electronic Data Capture platform and refined for comprehensibility and ease of use by patient focus groups. The electronic screener and physician-administered criteria were both administered to patients with known Chronic Overlapping Pain Conditions in a counter-balanced fashion to determine the level of agreement between methods. The expert panel identified screening items/body map regions and diagnostic criteria for all ten Chronic Overlapping Pain Conditions. Patients found the content comprehensible and the platform easy to use. Cohen's Kappa statistics suggested good agreement between the electronic Chronic Overlapping Pain Condition -Screener and criteria administered by a physician (κ=.813). The Chronic Overlapping Pain Condition -Screener is an efficient tool for screening multiple Chronic Overlapping Pain Condition -Screener s and has applicability to research studies, clinical trials, and clinical practice. PERSPECTIVE: Assessing Chronic Overlapping Pain Conditions remains a challenge for researchers and clinicians. The Chronic Overlapping Pain Condition - Screener is an efficient and logic-driven electronic tool that allows for the rapid screening assessment of ten Chronic Overlapping Pain Conditions. The instrument may have utility in research and clinical settings.

Abstract
Purpose: Post-thoracotomy pain syndrome (PTPS) and chronic postsurgical neuropathic pain (CPNP) were evaluated 4 months after thoracic surgery whether the approach was a posterolateral (PL) incision or the less invasive axillary (AX) one.

Methods: Patients, 79 in each group, undergoing a thoracotomy between July 2014 and November 2015 were analyzed 4 months after surgery in this prospective monocentric cohort study.

Results: More PL patients suffered PTPS (60.8% vs. 40.5%; p = 0.017) but CPNP was equally present (45.8% and 46.9% in the PL and AX groups). Patients with PTPS have more limited daily activities (p < 0.001) but a similar psychological disability (i.e., catastrophism). Patients with CPNP have an even greater limitation of daily activities (p = 0.007) and more catastrophism (p = 0.0002). Intensity of pain during mobilization of the homolateral shoulder at postoperative day 6 (OR = 1.40, CI 95% [1.13-1.75], p = 0.002); age (OR = 0.97 [0.94-1.00], p = 0.022), and presence of pain before surgery (OR = 2.22 [1.00-4.92], p = 0.049) are related to the occurrence of PTPS; while, height of hypoesthesia area on the breast line measured 6 days after surgery is the only factor related to that of CPNP (OR = 1.14 [1.01-1.30], p = 0.036).

Conclusion: Minimally invasive surgery was associated with less frequent PTPS, but with equal risk of CPNP. Pain before surgery and its postoperative intensity are associated with PTPS. This must lead to a more aggressive care of pain patients before surgery and of a better management of postoperative pain. CPNP can be forecasted according to the early postoperative height of hypoesthesia area on the breast line.

Abstract
Guidelines recommend consideration of modification, tapering, or discontinuation of long-term, full-agonist opioid therapy when harms outweigh benefits; one alternative to tapering or discontinuing full-agonist opioids for the management of chronic pain is switching to the partial agonist buprenorphine. As the use of buprenorphine for pain expands, understanding the patient experience during and after transition to buprenorphine is critical. We conducted 45- to 60-minute semi-structured qualitative interviews with 19 patients to understand the experiences of patients with chronic pain actively maintained on buprenorphine after previously receiving full-agonist, long-term opioid therapy. Patients were recruited from two medical centers via provider referral. Through thematic analysis, five overall themes were identified, including satisfaction with buprenorphine, the importance of preconceptions about buprenorphine, experiences with transitions, patient-provider communication, and potential contributions to racial disparities in pain care. While we heard a range of experiences, most patients were satisfied with buprenorphine, reporting either equivalent pain control to their previous regimens, or reporting less analgesia but improved functioning due to reduction in side effects (e.g., mental clarity). Patients also emphasized the importance of a non-judgmental, patient-centered approach, including education about the risks and benefits of buprenorphine. The few black patients interviewed all reported limited access to pain care, which is consistent with the well-documented existence of racial disparities in access to pain treatment. As buprenorphine is used more frequently for pain management, provider education focused on pain treatment disparities, patient-centered approaches informed by motivational interviewing, and increasing acceptance of buprenorphine as an option for pain are needed. PERSPECTIVE: Qualitative analyses of patient experiences transitioning from full-agonist opioids to buprenorphine for chronic pain revealed general satisfaction. Patients reflected on functioning, tradeoffs between analgesia and side effects, patient-centered care, and access to treatment, highlighting how future research should focus on outcomes valued by patients.

Abstract
Background: Despite widespread use of opioid therapy in outpatient palliative medicine, there is limited evidence supporting its efficacy and safety in the long term. Objectives: We sought to improve overdose risk scores, maintain pain reduction, and preserve patient function in a cohort with severe chronic pain as we managed opioid therapy for a duration of four years in an outpatient palliative care clinic. Design: Over four years, we provided ongoing goal-concordant outpatient palliative care, including opioid therapy, using quarterly clinical encounters for a patient cohort with chronic pain. Setting/Subjects: The project took place in the outpatient palliative medicine clinic of a regional cancer center in Orlando, Florida (United States). The subjects were a cohort group who received palliative care during the time period between July 2018 and October 2022. Measurements: Key metrics included treatment-related reduction in pain intensity, performance scores, and overall overdose risk scores. Secondary metrics included cohort demographics, average daily opioid use in morphine milligram equivalents and categorization of type of pain. Results: In 97 patients, we observed a stable mean treatment-related reduction in pain intensity of 4.9 out of 10 points over four years. The cohort showed a 2-point (out of 100) improvement in performance scores and an 81-point (out of 999) reduction in mean overall overdose risk score. Conclusions: We present evidence that providing outpatient palliative care longitudinally over four years offered lasting treatment-related reductions in pain intensity, preservation of performance status, and reduction in overall overdose risk.

Abstract
Spinal cord stimulation is an effective treatment for those experiencing chronic back and leg pain but requires a temporary evaluation period (SCSeval) before permanent implantation. We present real-world data from 7000 patients who underwent SCSeval while utilizing a mobile digital health platform for education, feedback, and outcomes collection during their surgical journey. We analyzed preoperative patient demographics, characterized patient pain profiles using the PROMIS-29 surveys, and calculated the rates of conversion from temporary to permanent SCS implantation. Between August 1, 2021 and March 2, 2023, 7000 patients (mean age 59.1, 59.6% female) underwent SCSeval procedures while utilizing a mobile application. Patients commonly experienced aching, sharp, stabbing, tingling, numb, and burning pain. Patients had tried multiple prior therapies and wanted to reduce their use of opioids and pain medications. Overall, 90.1% of patients had a successful SCSeval, and 80.4% of those converted to permanent implant, with the highest rates among those who underwent SCSeval in a hospital setting. There was significant improvement in all domains of pain as evaluated by pre-and-postoperative PROMIS-29 surveys. This study supports the use of digital health technology as part of the SCS journey to improve the patient experience and allow for robust patient reported outcomes collection. The overall rate of SCSeval to permanent SCS in our study of 72.4% was higher than national rates of 64%, suggesting that an app may allow clinicians to better quantify changes in chronic pain and provide more insight into choosing to implant SCS permanently. PERSPECTIVE: This article presents real world evidence from a digital health platform for therapy education and outcomes collection from patients undergoing spinal cord stimulation evaluation procedures. Such tools could allow for better pain characterization and allow for more nuanced tracking of patient outcomes among those with chronic pain.

Full citation:
Venkatraman V, Bharmi R, Coletti F, et al. Real World Characterization of Chronic Pain, Success Rates and Implant Rates: Evidence from a Digital Health Platform of Patients Undergoing Spinal Cord Stimulation Evaluations [published online ahead of print, 2023 Aug 2]. J Pain. 2023;S1526-5900(23)00470-4.

Abstract
Introduction: Ultrasound-guided peripheral nerve blockade is a common pain management strategy to decrease perioperative pain and opioid/general anesthetic use. In this article our goal was to systematically review publications supporting upper extremity nerve blocks distal to the brachial plexus. We assessed the efficacy and safety of median, ulnar, radial, suprascapular, and axillary nerve blocks by reviewing previous studies.

Methods: We searched MEDLINE and Embase databases to capture studies investigating these nerve blocks across all specialties. We screened titles and abstracts according to agreed-upon inclusion/exclusion criteria. We then conducted a hand search of references to identify studies not found in the initial search strategy.

Results: We included 20 studies with 1,273 enrolled patients in qualitative analysis. Both anesthesiology (12, 60%) and emergency medicine (5, 25%) specialties have evidence of safe and effective use of radial, ulnar, median, suprascapular, and axillary blocks for numerous clinical applications. Recently, multiple randomized controlled trials show suprascapular nerve blocks may result in lower pain scores in patients with shoulder dislocations and rotator cuff injuries, as well as in patients undergoing anesthesia for shoulder surgery.

Conclusion: Distal upper extremity nerve blocks under ultrasound guidance may be safe, practical strategies for both acute and chronic pain in perioperative, emergent, and outpatient settings. These blocks provide accessible, opioid-sparing pain management, and their use across multiple specialties may be expanded with increased procedural education of trainees.

Abstract
Background: There is a significant research gap with respect to the long-term sustainability of psychological treatment effects in chronic pain patients. This study aimed to investigate long-term treatment effects of two psychological treatments: cognitive behavioural therapy (CBT) as a broad-spectrum approach and exposure as a specific intervention for fear-avoidant pain patients.

Methods: Patients with chronic low back pain were randomized to CBT or exposure in vivo. Long-term follow-up (LTFU) data were available for 64 patients up to 8 years after treatment, with a response rate of 73%. The primary outcomes were pain-related disability and pain intensity and secondary outcomes were emotional distress, psychological flexibility, catastrophizing and pain-related fear. The data analysis was performed with longitudinal multilevel modelling.

Results: Multilevel analyses showed improvements in all primary outcomes as well as all secondary outcomes from pre-treatment to LTFU for both treatments. The mean proportion of cases meeting reliable and clinical improved criteria in all primary outcome was 36% (range: 22%-46%) in the exposure group and 50% (range: 33%-60%) in the CBT group. Dropout analyses revealed significantly higher deterioration rates over time. Pre-treatment to LTFU effect sizes of the primary outcomes ranged from 0.54 to 1.59.

Conclusions: Our results indicate that the effects of psychological treatments might be stable over several years. Treatment gains for exposure as a stand-alone treatment seem to be of shorter duration than a general CBT intervention. Thus, psychological treatments might offer a promising and sustainable long-term perspective for patients with chronic back pain.

Significance: The long-term stability of treatment effects is a highly neglected issue despite its inherent importance in the context of chronic pain. This study is the first to investigate treatment effects of cognitive behavioural therapy and in vivo exposure in chronic back pain sufferers up to 8 years after treatment. The findings contribute to an understanding of the sustainability of psychological cognitive behavioural therapy-based intervention effects.

Abstract
Objective: The co-existence of chronic pain conditions with anxiety and/or depression is common in the general population but poorly described during pregnancy. In this study, we sought to describe trends in chronic pain among a sample of delivering people and describe the co-existence of chronic pain with anxiety and/or depression among delivering people.

Methods: This cross-sectional study used data from Optum's de-identified Clinformatics® Data Mart Database between 2008 and 2021, for delivering persons with coverage by single employer-based health plan. We computed predicted margins from generalized estimating equations to determine the marginal predicted probability of chronic pain among all delivering and non-delivering persons who identify as women with and without diagnosed anxiety and/or depression.

Abstract
Objective: Predictors of pain persistence have been identified among patients undergoing treatment for chronic pain or related conditions, but correlates of pain persistence in the general population remain underexplored. We identify socioeconomic variables associated with pain onset or persistence over a 6-10 year period in a nationally representative cohort.

Methods: Using panel data from the National Longitudinal Survey of Youth-1997, we examined the presence of pain interference at age 29 and chronic pain at ages 35-39. Persistent pain was defined as pain present at both interview timepoints; new onset pain was defined as pain not reported at age 29, but present at ages 35-39; and transient pain was defined as experiencing pain interference at age 29 with no report of chronic pain at ages 35-39.

Abstract
Chronic pain acceptance is a psychological process consistently linked with improved functional outcomes. However, existing research on this construct has not considered the role of racial or ethnic background, despite growing evidence of racialized disparities in pain experience and treatment. This study aimed to examine racial differences in chronic pain acceptance, as measured by the Chronic Pain Acceptance Questionnaires (CPAQ), in a multicultural sample of individuals with chronic low back pain (CLBP; N = 137 -- 37.2% White, 31.4% Hispanic, and 31.4% Black/African American). We further sought to examine moderating effects of discrimination, pain-related perceived injustice (PI), and just world belief (JWB). Analyses consisted of cross-sectional one-way analyses of variance (ANOVAs) with Bonferroni-corrected post-hoc comparisons, followed by regression models with interaction terms, main effects, and relevant covariates. Results indicated higher scores on the CPAQ for White individuals compared to Black or Hispanic individuals. Significant interactions were noted between race/ethnicity and JWB in predicting pain acceptance, after controlling for demographic and pain-related variables, such that the positive association between JWB and pain acceptance was significant for White participants only. Race/ethnicity did not show significant interactions with PI or prior racial discrimination. Findings highlight racial differences in levels of chronic pain acceptance, an adaptive pain coping response, and a stronger JWB appears to have a positive impact on pain acceptance for White individuals only. Results further confirm that members of disadvantaged racial groups may be more susceptible to poorer pain adjustment, which is the result of complex, multi-level factors. PERSPECTIVE: This study identifies racial differences in levels of pain acceptance, an adaptive psychological response to chronic pain, such that White individuals with chronic low back pain demonstrate higher levels of pain acceptance. The article further explores the impacts of intrapersonal and sociocultural variables on racial differences in pain acceptance.

Keywords: Chronic pain; Ethnic differences; Pain acceptance; Psychological factors; Racial differences.

Abstract
A spinal cord stimulator is an important long-term treatment modality for refractory chronic pain of multiple etiologies. Hardware-related complications remain known adverse events associated with this intervention. Understanding the risk factors for development of such complications is important for optimizing the efficacy and longevity of spinal cord stimulators. This case report highlights an uncommon case of implantable pulse generator site calcification that was discovered incidentally on spinal cord stimulator explant.

Keywords: Chronic pain; mental defeat; predictor; prospective associations; suicide risk.

Full citation:
Neumann N, Domin M, Schmidt CO, Lotze M. Chronic pain is associated with less grey matter volume in the anterior cingulum, anterior and posterior insula and hippocampus across three different chronic pain conditions [published online ahead of print, 2023 Jun 27]. Eur J Pain. 2023;10.1002/ejp.2153

Keywords: Chronic postsurgical pain; General anesthesia; Long-term analgesic and opioid use; Old age; Young age.

Keywords: Chronic pain; cognitive therapy; hypnosis; low back pain; moderators.

The preferential use of a scalpel (SCT) or puncture techniques (PCT) for cricothyrotomy remains a controversial topic. This is a systematic review and meta-analysis comparing puncture cricothyrotomy with scalpel cricothyrotomy using overall success rate, first-time success rate, and time taken to perform the procedure as the primary outcome together with complications as a secondary outcome.

Keywords: Conservative management; Greater trochanteric pain syndrome; Visual analogue pain score.

Keywords: Primary Care; Pain management.

Keywords: anxiety; circadian preference; depression; insomnia; pain.

‘Anaesthesia, Pain & Intensive Care’, is an international, peer reviewed journal. Registered by Pakistan Medical & Dental Council and recognized by Higher Education Commission of Pakistan.

Anaesthesia, Critical Care & Pain Medicine (formerly Annales Françaises d'Anesthésie et de Réanimation) publishes in English the highest quality original material, both scientific and clinical, on all aspects of anaesthesia, critical care & pain medicine.

This open access journal is the official Journal of the Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM), covering clinical and basic research, education, patient care, health economics, and policy to inform all practitioners in pain management, such as anesthesiologists, interventional pain physicians, neurosurgeons, neurologists, and any specialists who are interested in pain medicine.

British Journal of Pain is a peer-reviewed quarterly British journal with an international multidisciplinary Editorial Board. The journal publishes Original Papers and Reviews on all major aspects of pain and pain management reflecting the body of evidence of the topic and suitable for a multidisciplinary readership. Where empirical evidence is lacking, the reviews reflect the generally held opinions of experts in the field.

The Clinical Journal of Pain explores all aspects of pain and its effective treatment, bringing you the insights of leading anesthesiologists, surgeons, internists, neurologists, orthopedists, psychiatrists and psychologists, clinical pharmacologists, and physical and rehabilitation therapists.

A multi-disciplinary, international journal that aims to be a global forum on all aspects of pain research and pain management. The journal publishes clinical and basic science research papers relevant to all aspects of pain and its management.

The Journal of Headache and Pain is a peer-reviewed open access journal specifically dedicated to researchers involved in all aspects of headache and related pain syndromes, including epidemiology, public health, basic science, translational medicine, clinical trials and real-world data.

This journal aims to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research. Other content includes invited critical reviews, invited commentaries on reviews, and exceptional case studies.

This journal provides a forum for the publication of the latest clinical research and best practices related to the relief of illness burden among patients afflicted with serious or life-threatening illness.

Neurobiology of Pain is an international journal for the publication of basic and translational research on the mechanisms of acute and chronic pain. It focuses on experimental studies of pain mechanisms at every level from molecular and cellular to brain imaging and behavioural.

PAIN® is the official publication of the International Association for the Study of Pain® (IASP®). PAIN® publishes original research on the nature, mechanisms, and treatment of pain and provides a multidisciplinary forum for the dissemination of research in the basic and clinical sciences.

Regional Anesthesia & Pain Medicine, the official publication of the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine), is a monthly journal that publishes peer-reviewed scientific and clinical studies to advance the understanding and clinical application of regional techniques for surgical anesthesia and postoperative analgesia. Coverage includes intraoperative regional techniques, perioperative pain, chronic pain, obstetric anesthesia, paediatric anesthesia, outcome studies, and complications.

The Scandinavian Journal of Pain (SJPAIN) publishes internationally relevant articles on all aspects of pain. The journal is the official quarterly publication of the Scandinavian Association for the Study of Pain and serves as a forum for original research on the nature of pain, pain mechanisms, and pain management.

Incorporated into Journal of Critical Care.

One of the case studies looks at the 'Turning Pain into Gain' program for people living with chronic pain. The program is delivered via group sessions, one-on-one clinical service assessments and allied health services, and support staff include volunteers who completed the program in the past. Evaluation of the program found that it improved participants’ ability to undertake various day-to-day activities, including exercise, household chores and leisure activities, and reduced hospitalisations by 78%.