Pain medicine essentials: Articles

Abstract
Workplace violence is any physical assault, threatening behavior or other verbal abuse directed toward persons at work or in the workplace. The incidence of workplace violence in healthcare settings in general and more specifically the pain clinic is thought to be underestimated due to hesitancy to report, lack of support from management and healthcare systems, and lack of institutional policies as it relates to violence from patients against healthcare workers. In the following article, we explore risk factors that place clinicians at risk of workplace violence, the cost and impact of workplace violence, how to build a violence prevention program and lastly how to recover from violence in the practice setting.

Abstract
Introduction: Temporomandibular disorders (TMD) is a multifactorial group of musculoskeletal disorders often with combined etiologies that demand different treatment plans. While pain is the most common reason why patients decide to seek help, TMD is not always painful. Pain is often described by patients as a headache, prompting patients to seek the help of neurologists, surgeons, and ultimately dentists. Due to the unique characteristics of this anatomical area, appropriate diagnostic tools are needed, as well as therapeutic regimens to alleviate and/or eliminate the pain experienced by patients. Aim of the Study. The aim of this study is to collect and organize information on the diagnosis and treatment of pain in TMD, through a review of the literature supplemented by our own clinical experience. Material and Methods. The study was conducted by searching scientific databases PubMed, Scopus, and Google Scholar for documents published from 2002-2022. The following keywords were used to build the full list of references: TMD, pain, temporomandibular joint (TMJ), TMJ disorders, occlusal splint, relaxing splints, physiotherapy TMD, pharmacology TMD, natural therapy TMD, diagnostic criteria for TMD, and DC/TMD. The literature review included 168 selected manuscripts, the content of which was important for pain diagnosis and clinical treatment of TMD.

Results: An accurate diagnosis of TMD is the foundation of appropriate treatment. The most commonly described treatments include physiotherapy, occlusal splints therapy, and pharmacological treatment tailored to the type of TMD.

Conclusions: Based on the literature review and their own experience, the authors concluded that there is no single ideal form of pain therapy for TMD. Treatment of TMD should be based on a thorough diagnostic process, including the DC/TMD examination protocol, psychological evaluation, and cone beam computer tomography (CBCT) imaging. Following the diagnostic process, once a diagnosis is established, a treatment plan can be constructed to address the patient's complaints.

This article is being published concurrently in Journal of Pain, PAIN, European Journal of Pain, Pain Medicine, Canadian Journal of Pain, Journal of Pain Research, Clinical Journal of Pain, and PAIN Reports. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Citation from any of the journals can be used when citing this article.

Abstract
Background: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine.

Objectives/study design: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists.

Methods: In this study, all 114 pain program directors listed on the Accreditation Council for Graduate Medical Education (ACGME) website, or their administrative assistants were directly contacted via email. All email addresses were obtained from the ACGME website. The survey opened in September 2021, with reminder emails sent before the closing of the survey in December 2021. A final reminder email was sent 4 weeks prior to the closing of the survey.

Results: Of all the respondents, 79 (89.77%) were currently practicing pain medicine, and 9 (10.23%) were no longer practicing pain medicine.

Limitations: Our study has a major limitation as we are unable to determine the response rate and are limited in the data points gathered.

Conclusion: We hope this study will allow for pain medicine fellowship program directors to improve recruitment and retention of pain fellows in the field while addressing the pros and cons of future career aspirations with anesthesiology residents prior to fellowship selection. A larger, more thorough study with an exact response rate can compare the various outcomes based upon different types of settings, such as private practice, partnership, and academia, as well as geographical locations.

Abstract
Objectives: Trauma (i.e., musculoskeletal injury from a blunt or penetrating force) can change the trajectory of a person's life. Patients often experience chronic pain, reduced quality of life, long-term opioid therapy, and psychiatric comorbidities after trauma surgery. This case report presents clinical outcomes of four patients who received postsurgical pain care in a transitional pain service (TPS) that provides long-term coordinated multimodal pain care, opioid tapering plans, and psychiatric care.

Methods: The Personalized Pain Program (PPP) measures prescription opioid use and patient-reported outcomes: pain severity and pain interference (Brief Pain Inventory), pain catastrophizing (Pain Catastrophizing Scale), insomnia severity (Insomnia Severity Index), physical and mental health functioning (SF-12 pre-COVID-19; SF-36 during COVID-19 pandemic) at initial and subsequent clinic visits.

Results: All four patients reduced their postsurgical opioid use with concurrent reductions in pain and improved functioning while receiving postoperative care in the PPP (average length of treatment: 2.8 years). Psychiatric co-treatment addressed the onset or exacerbation of mental health comorbidities following trauma.

Conclusions: Long-term multidisciplinary pain care may improve post-trauma recovery and reduce risks of long-term opioid therapy and disability. Prospective studies are needed to evaluate the effectiveness of TPSs for patients undergoing trauma surgery.

Abstract
Objectives: Comorbid with chronic pain are negative emotions, anger being particularly salient. To evaluate specific relationships between pain and anger, the present study deconstructed anger into five parameters and dichotomized pain into sensory vs. affective components. Hypotheses were (i) anger parameters would be significantly and positively correlated with affective pain more so than with sensory pain, and (ii) individual parameters would be differentially related to pain components.

Methods: The Anger Parameters Scale (APS) was used to rate five parameters of anger: frequency, duration, intensity, latency, and threshold. Also rated was the physical sensation of pain and the degree of distress from pain. The volunteer sample comprised n=51 chronic pain patients, varying in ethnicity/race and educational level.

Results: Descriptive statistics revealed: APS total M=71.52, SD=16.68, Sensory pain M=6.27, SD=2.15, Affective pain M=5.76, SD=2.28. Sensory and affective pain were highly correlated, r=0.70. APS total was significantly associated with affective pain (r=+0.28) but hardly with sensory pain (r=0.12). Two anger parameters significantly correlated with affective pain: anger frequency (r=+0.30, p<0.05) and anger threshold (r=+0.33, p<0.05). Secondarily, certain educational levels (but not gender and ethnicity/race) were associated with significantly higher APS total scores.

Conclusions: Scores for all variables were in the mid-range. As hypothesized, anger was more strongly correlated with distress/suffering of pain than with physical sensation of pain, though both pain components were closely coupled. Specific findings regarding frequency and threshold imply that being angry often and being oversensitive to provocation are associated with greater distress in this context. In deconstructing anger and dichotomizing pain, the present study extends previous research by elaborating on what aspects of anger are most related to which components of pain. Moreover, certain educational levels with higher levels of anger may need special attention. Further research could examine if treatment of anger might lead to corresponding changes in chronic pain.

Abstract
Chronic pain and sleep problems frequently co-occur. Pain itself disturbs sleep, but other factors may also contribute to sleep problems in pain patients. This cross-sectional study of 473 patients (69.9% female, mean age 47 years) entering tertiary pain management compared normally sleeping pain patients with those having recurring sleep problems to determine the relationship between pain and sleep. Groups were compared for pain and pain aetiology, pain-related anxiety, childhood adversities, use of sleep and pain medications, self-reported diseases, and sleep disorders. Furthermore, the association of pain-related anxiety (cognitive anxiety, escape/avoidance, fear, and physiological anxiety) with more disturbing sleep problems was investigated in the whole cohort. The main results were that those with sleep problems more often reported multiple health conditions than those sleeping normally (depression 31.6% vs 5.0%; angina pectoris 6.5% vs 0.0%; asthma 19.6% vs 1.7%; low back problems 55.1% vs 23.3%; joint disease other than rheumatoid arthritis 32.3% vs 18.3%). Accumulations of 5 or more childhood adversities were more often present in those with sleep problems. Restless legs symptoms were more common in those with sleep problems than those sleeping normally (33.2% vs 11.7%). Patients having sleep problems reported more use of sleep and pain medications than those sleeping normally. Findings about pain-related anxiety suggest physiological reactions as significant factors for increased sleep disturbances. These factors need to be addressed in the management of the comorbidity of pain and sleep problems, and research to understand mechanisms in these is sorely needed.

Abstract
Objective: This is the fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy).

Methods: Expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included. The literature review was supplemented with knowledge gained from extensive empirical clinical experience, particularly in areas where high-quality evidence to guide therapy is lacking.

Results: The research quality, clinical relevance, and "state of the art" of diagnostic criteria or treatment modalities are discussed, sometimes in considerable detail with an eye to the expert practitioner in each therapeutic area. Levels of evidence are mentioned when available, so that the practitioner can better assess and analyze the modality under discussion, and if desired, to personally consider the citations. Tables provide details on characteristics of studies in different subject domains described in the literature.

Conclusions: In the humanitarian spirit of making the most of all current thinking in the area, balanced by a careful case-by-case analysis of the risk/cost vs benefit analysis, the authors offer these "practical" guidelines.

Abstract
Background: Habituation is a response decrement resulting from repeated stimuli. Reduced habituation to noxious stimuli is considered to be a proxy for central sensitization in subjects with chronic pain. Despite numerous investigations of pain habituation in relation to central sensitization, there is no consensus on the most sensitive and reliable readout, as well as analysis approach. Therefore, this study compared the usability and reliability of different readouts and habituation analysis approaches to measure pain habituation in response to repetitive heat simulation.

Methods: Three blocks of 20 contact heat stimuli were applied on the volar forearm of 20 healthy subjects on two separate visits. Habituation was assessed by three different readouts: pain ratings, contact heat evoked potentials (CHEPs) and heat-induced sympathetic skin responses (SSRs). In addition, two different habituation analysis approaches were used: between the three stimulation blocks (between-block) and within the first stimulation block (within-block).

Results: Significant between-block habituation for SSRs (p < 0.001), but not for pain ratings (p = 1.000) and CHEPs (p = 0.078) was found. There was significant within-block habituation for pain ratings (p = 0.012) and SSRs (p < 0.001), but not for CHEPs (p = 0.246). Only the between-block habituation of heat-induced SSR was reliable between the two visits (first to second block: intraclass correlation coefficient (ICC) = 0.58, p = 0.030; first to third block: ICC = 0.64, p = 0.015).

Conclusion: Heat-induced SSR as a measure of pain-autonomic interaction revealed the strongest pain habituation and showed highest test-retest reliability.

Abstract
Background: We estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. We also consider the effect of the perceived abuse potential of the medication on these variables.

Methods: This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication.

Results: The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error (SE) of 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.1% (SE: 2.3%) and 7.1% (SE: 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (SE: 4.6%) and 4.7% (SE: 1.2%), respectively. The most common period for attrition is between phase 3 and approval.

Discussion: Our data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.

Importance: Limiting opioid overprescribing in the emergency department (ED) may be associated with decreases in diversion and misuse.

Objective: To review and analyze interventions designed to reduce the rate of opioid prescriptions or the quantity prescribed for pain in adults discharged from the ED.

Data sources: MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Controlled Register of Trials databases and the gray literature were searched from inception to May 15, 2020, with an updated search performed March 6, 2021.

Study selection: Intervention studies aimed at reducing opioid prescribing at ED discharge were first screened using titles and abstracts. The full text of the remaining citations was then evaluated against inclusion and exclusion criteria by 2 independent reviewers.

Data extraction and synthesis: Data were extracted independently by 2 reviewers who also assessed the risk of bias. Authors were contacted for missing data. The main meta-analysis was accompanied by intervention category subgroup analyses. All meta-analyses used random-effects models, and heterogeneity was quantified using I2 values.

Main outcomes and measures: The primary outcome was the variation in opioid prescription rate and/or prescribed quantity associated with the interventions. Effect sizes were computed separately for interrupted time series (ITS) studies.

Results: Sixty-three unique studies were included in the review, and 45 studies had sufficient data to be included in the meta-analysis. A statistically significant reduction in the opioid prescription rate was observed for both ITS (6-month step change, -22.61%; 95% CI, -30.70% to -14.52%) and other (odds ratio, 0.56; 95% CI, 0.45-0.70) study designs. No statistically significant reduction in prescribed opioid quantities was observed for ITS studies (6-month step change, -8.64%; 95% CI, -17.48% to 0.20%), but a small, statistically significant reduction was observed for other study designs (standardized mean difference, -0.30; 95% CI, -0.51 to -0.09). For ITS studies, education, policies, and guideline interventions (6-month step change, -33.31%; 95% CI, -39.67% to -26.94%) were better at reducing the opioid prescription rate compared with prescription drug monitoring programs and laws (6-month step change, -11.18%; 95% CI, -22.34% to -0.03%). Most intervention categories did not reduce prescribed opioid quantities. Insufficient data were available on patient-centered outcomes such as pain relief or patients' satisfaction.

Conclusions and relevance: This systematic review and meta-analysis found that most interventions reduced the opioid prescription rate but not the prescribed opioid quantity for ED-discharged patients. More studies on patient-centered outcomes and using novel approaches to reduce the opioid quantity per prescription are needed.

Abstract
Background: Monitoring children's recovery postoperatively is important for routine care, research, and quality improvement. Although telephone follow-up is common, it is also time-consuming and intrusive for families. Using SMS messaging to communicate with families regarding their child's recovery has the potential to address these concerns. While a previous survey at our institution indicated that parents were willing to communicate with the hospital by SMS, data on response rates for SMS-based postoperative data collection is limited, particularly in pediatric populations.

Aims: We conducted a feasibility study with 50 completed pain profiles obtained from patients at Perth Children's Hospital to examine response rates.

Methods: We collected and classified daily average pain (0-10 parent proxy score) on each day after tonsillectomy until pain-free for two consecutive days.

Results: We enrolled 62 participants and recorded 50 (81%) completed pain profiles, with 711 (97.9%) of 726 requests for a pain score receiving a response. Two families (3%) opted out of the trial, and 10 (16%) were lost to follow-up. Responses received were classified automatically in 92% of cases. No negative feedback was received, with a median (range) satisfaction score of 5 on a 5-point Likert scale (1 = very unhappy, 5 = very happy).

Conclusions: This methodology is likely to generalize well to other simple clinical questions and produce good response rates in further similar studies. We expect SMS messaging to permit expanded longitudinal data collection and broader investigation into patient recovery than previously feasible using telephone follow-up at our institution.

COMMENTARY. No abstract available.

Abstract
Objectives: Societal and health system pressures associated with the COVID-19 pandemic exacerbated the burden of chronic pain and limited access to pain management services for many. Online multidisciplinary pain programs offer an effective and scalable treatment option, but have not been evaluated within the context of COVID-19. This study aimed to investigate the uptake and effectiveness of the Reboot Online chronic pain program before and during the first year of the COVID-19 pandemic.

Methods: Retrospective cohort analyses were conducted on routine service users of the Reboot Online program, comparing those who commenced the program during the COVID-19 pandemic (March 2020-March 2021), to those prior to the pandemic (April 2017-March 2020). Outcomes included the number of course registrations; commencements; completion rates; and measures of pain severity, interference, self-efficacy, pain-related disability and distress.

Results: Data from 2585 course users were included (n = 1138 pre-COVID-19 and n = 1447 during-COVID-19). There was a 287% increase in monthly course registrations during COVID-19, relative to previously. Users were younger, and more likely to reside in a metropolitan area during COVID-19, but initial symptom severity was comparable. Course adherence and effectiveness were similar before and during COVID-19, with moderate effect size improvements in clinical outcomes post-treatment (g = 0.23-0.55).

Discussion: Uptake of an online chronic pain management program substantially increased during the COVID-19 pandemic. Program adherence and effectiveness were similar pre- and during-COVID. These findings support the effectiveness and scalability of online chronic pain management programs to meet increasing demand.

Objectives: OxyContin® was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin's reformulation on overdose risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care.

Methods: Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (ER morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation changes in OD rates for OxyContin versus comparators.

Results: 297,836 individuals were dispensed OxyContin and 659,673 individuals were dispensed a primary comparator across the three databases. Overall, there was little or no difference in the temporal change in OD incidence in comparators versus OxyContin (Medicaid: adjusted ratio-of-rate-ratios (aRoRs) ranging from 0.90 to 1.05; MarketScan/HIRD: aRoR ranging from 1.10 to 1.22). However, restriction to person-time without concomitant opioid use revealed a modestly greater reduction in OD incidence over time during OxyContin use, as the aRoRs comparing the primary comparators to OxyContin ranged from 1.06 to 1.30 in Medicaid and from 1.64 to 1.85 in MarketScan/HIRD.

Discussion: This study did not detect an overall effect of the OxyContin reformulation on OD in insured patients under regular medical care. There is a suggestion of a modestly reduced OxyContin-associated OD risk following the reformulation but only in commercially-insured individuals receiving single-opioid regimens.

This systematic review aims to review clinical studies on the use of ketamine infusion for patients with treatment-resistant complex regional pain syndrome (CRPS). The following systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021228470). Studies for the systematic review were identified through three databases: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Reviews. Inclusion criteria for studies consisted of randomized clinical trials or cohort studies that conducted trials on the use of ketamine infusion for pain relief in patients with CRPS. Exclusion criteria for studies included any studies that were systematic reviews, meta-analyses, case reports, literature reviews, or animal studies. In the included studies, the primary outcome of interest was the post-drug administration pain score. In this systematic review, 14 studies met the inclusion criteria and were reviewed. In these studies, the dosage of ketamine infusion used ranged from 0.15 mg/kg to 7 mg/kg with the primary indication being the treatment of CRPS. In 13 of the studies, ketamine infusion resulted in a decrease in pain scores and relief of symptoms. Patients who received ketamine infusion for treatment-resistant CRPS self-reported adequate pain relief with treatment. This suggests that ketamine infusion may be a useful form of treatment for patients with no significant pain relief with other conservative measures. Future large-scale studies, including randomized double-blind placebo-controlled trials on the use of ketamine infusion for CRPS, must be conducted in a large-scale population to further assess the effectiveness of ketamine infusion in these populations.

Over the last decades public discussion of opioids has changed radically. Opioid was once a word largely restricted to professional medical and pharmacological use for the treatment and management of pain. But propelled by the rapidly growing international wave of opioid use and overuse, it is now part of a much wider public discussion that covers more than pain medicine: dependency, addiction, over-prescription and oversupply, recreational drug use, and criminal drug trafficking. The word opioid is now controversial and value-laden. A key component of the developing views and values about opioids is carried by language, both written and spoken: on radio and television, in the social media, but also between healthcare professionals and patients, where communicating about pain in a context of emotionally and value-charged images of opioids can be challenging. This paper analyses aspects of the language of opioids. We document the shift from medical to addiction meanings and uses in the key term opioid, together with narcotic, drug, heroin, and to a lesser degree opiate and morphine. These changes follow four chronological phases in attitudes to pain and its treatment: traditional medical approaches to pain; pain being recognised as an under-treated 'fifth vital sign'; the pharmacological and medical promotion of opioid use for treating pain, especially chronic pain; and the current reaction where opioid has become a pejorative and emotive term, closely connected to words like epidemic and addiction. We investigate whether and how a less charged and more balanced discourse might be possible.

Abstract
Exercise and pain neuroscience education (PNE) have both been used as standalone treatments for chronic musculoskeletal pain. The evidence supporting PNE as an adjunct to exercise therapy is growing but remains unclear. The aim of this systematic review and meta-analysis was to evaluate the effect of combining PNE and exercise for patients with chronic musculoskeletal pain, when compared with exercise alone. A systematic search of electronic databases was conducted from inception to November 6, 2020. A quality effects model was used to meta-analyze outcomes where possible. Five high-quality randomized controlled studies (n = 460) were included in this review. The PEDro scale was used to assess the quality of individual studies, and Grading of Recommendations, Assessment, Development, and Evaluation analysis was conducted to determine the quality of evidence for each outcome. Meta-analyses were performed for pain intensity, disability, kinesiophobia, and pain catastrophizing using data reported between 0 and 12 weeks postintervention. Long-term outcomes (>12 weeks) were only available for 2 studies and therefore were not suitable for meta-analysis. Meta-analysis revealed a significant difference in pain (weighted mean differences, -2.09/10; 95% confidence interval [CI], -3.38 to -0.80; low certainty), disability (standardized mean difference, -0.68; 95% CI, -1.17 to -0.20; low certainty), kinesiophobia (standardized mean difference, -1.20; CI, -1.84 to -0.57; moderate certainty), and pain catastrophizing (weighted mean differences, -7.72; 95% CI, -12.26 to -3.18; very low certainty) that favoured the combination of PNE and exercise. These findings suggest that combining PNE and exercise in the management of chronic musculoskeletal pain results in greater short-term improvements in pain, disability, kinesiophobia, and pain catastrophizing relative to exercise alone.

Abstract
Objective: The placebo effect is important in determining the outcome of the treatment of pain for which expectancy and context are the main contributors. The variable success of thermal neurotomy spinal pain procedures is often seen as evidence of the placebo effect. Conversely, proponents of pain procedures explain poorer outcomes by technical procedure deficiencies, including inadequate diagnosis. This cohort study set out to determine whether patient expectancy is a contributing factor in the outcome of thermal neurotomy to the cervical, thoracic, and lumbar zygapophysial and sacroiliac joints.

Design: This single-practitioner, single-site retrospective analysis of prospectively gathered cohort data of 549 patients evaluated the impact of patient preprocedure expectancy (rated on a simple 0-10 or 0-4 numerical rating scale) on outcomes in a large consecutive series of patients who had undergone thermal neurotomy treatment between 2009 and 2019. In addition, a portion of patients were asked to what extent they hoped for or desired a good outcome.

Results: Successful pain relief (≥75% reduction from baseline) was not associated with a higher preprocedure expectancy than were failed procedures. Hope and desire demonstrated no impact on the positive or negative impact of the procedure.

Conclusions: Altogether, patient expectation of outcome, hope, and desire are not associated with the outcome of effective pain relief by thermal neurotomy that has been performed to the appropriate and commonly available technical standards. Further work is needed to determine the influence of patient expectation across a range of pain intervention modalities.

Abstract
Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. The study was conducted in 4 pain clinics in Cuba, India, and New Zealand. Twenty-one clinicians used the ICD-11 to diagnose and code n = 353 patients with chronic pain. Of these, 111 were assessed by 2 clinicians, and Fleiss' kappa was calculated to establish interrater reliability for any diagnosis assigned to ≥15 patients. The clinicians rated the clinical utility of all diagnoses. The interrater reliability could be calculated for 11 diagnoses. It was substantial for 10 diagnoses and moderate for 1 (kappa: 0.596-0.783). The mean clinical utility of the ICD-11 chronic pain diagnoses was rated as 8.45 ± 1.69/10. Clinical utility was rated higher for ICD-11 than for the commonly used classification systems (P < 0.001, η2 = 0.25) and differed between all centers (P < 0.001, η2 = 0.60). The utility of the ICD-11 diagnoses was rated higher than the commonly used diagnoses in Dunedin and Havana, and no difference was found in Kolkata and Hyderabad. The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings.

Opioids remain the major drug class for the treatment of acute, chronic and cancer pain, but have major harmful effects such as dependence and opioid-induced ventilatory impairment. Although no new typical opioids have come onto the market in the past almost 50 years, a plethora of new innovative formulations has been developed to meet the clinical need. This review is intended to shed light on new understanding of the molecular pharmacology of opioids, which has arisen largely due to the genomic revolution, and what new drugs may become available in the coming years. Atypical opioids have and are being developed which not only target the mu opioid receptor but other targets in the pain pathway. Biased mu agonists have been developed but remain 'unbiased' clinically. The contribution of drugs targeting non-mu opioid receptors either alone or as heterodimers shows potential promise but remains understudied. That gene splice variants of the mu opioid receptor produce multiple receptor isoforms in different brain regions, and may change with pain chronicity and phenotype, presents new challenges but also opportunities for precision pain medicine. Finally, that opioids also have pro-inflammatory effects not aligned with mu opioid receptor binding affinity implicates a fresh understanding of their role in chronic pain, whether cancer or non-cancer. Hopefully, a new understanding of opioid analgesic drug action may lead to new drug development and better precision medicine in acute and chronic pain relief with less patient harm.

Background: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial.

Methods: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement.

Results: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation.

Conclusions: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Abstract
Objective: To conduct a comprehensive search for evidence whether Central Sensitization following an injury can act as a persistent autonomous pain generator after the inducing injury has healed.

Methods: We searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence.

Results: Fourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found.Sixty-two publications were judged to provide weak evidence for a negative answer, and nine judged to provide strong evidence.Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of Central Sensitization in man:(i) Inappropriate extrapolation, in many publications, of laboratory animal data to humans.(ii) Failure to demonstrate the absence of peripheral pain generators which might be perpetuating Central Sensitization.(iii) Many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and Central Sensitization Inventory.

Conclusions: We found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed.Our review has also shown that the evidential basis for the diagnosis of CS in individual patients is seriously in question.

Pain represents an embodied experience, wherein inferences are not only drawn from external sensory inputs, but also from bodily states. Previous research has demonstrated that a placebo administered to an embodied rubber hand can effectively induce analgesia, providing first evidence that placebos can work even when applied to temporarily embodied, artificial body parts. Using a heat pain paradigm, the present study investigates placebo analgesia and pain perception during virtual embodiment. We examined whether a virtual placebo (a sham heat protective glove) can successfully induce analgesia, even when administered to a virtual body. The analgesic efficacy of the virtual placebo to the real hand (augmented reality setting) or virtual hand (virtual reality setting) was compared to a physical placebo administered to the own, physical body (physical reality setting). Furthermore, pain perception and subjective embodiment were compared between settings. In this mixed design experiment, healthy participants (n=48) were assigned to either an analgesia-expectation or control-expectation group, where subjective and objective pain was measured at pre- and post-intervention time points. Results demonstrated that pre-intervention pain intensity was lower in the virtual reality setting, and that participants in the analgesia-expectation condition, after the intervention, exhibited significantly higher pain thresholds, and lower pain intensity and unpleasantness ratings than control-expectation participants, independent of the setting. Our findings show that a virtual placebo can elicit placebo analgesia comparable to that of a physical placebo, and that administration of a placebo does not necessitate physical bodily interaction to produce analgesic responses.

When pain persists beyond healing time and becomes a "false alarm" of bodily threat, protective strategies, such as avoidance, are no longer adaptive. More specifically, generalization of avoidance based on conceptual knowledge may contribute to chronic pain disability. Using an operant robotic-arm avoidance paradigm, healthy participants (N=50), could perform more effortful movements in the threat context (e.g. pictures of outdoor scenes) to avoid painful stimuli, whereas no pain occured in the safe context (e.g. pictures of indoor scenes). Next, we investigated avoidance generalization to conceptually related contexts (i.e. novel outdoor/indoor scenes). As expected, participants avoided more when presented with novel contexts conceptually related to the threat context than in novel exemplars of the safe context. Yet, exemplars belonging to one category (outdoor/indoor scenes) were not interchangeable; there was a generalization decrement. Posthoc analyses revealed that contingency-aware participants (n=27), but not non-aware participants (n=23), showed the avoidance generalization effect and also generalized their differential pain-expectancy and pain-related fear more to novel background scenes conceptually related to the original threat context. In contrast, the fear-potentiated startle response was not modulated by context.

Little is known about the mechanisms by which pain catastrophizing may be associated with opioid use outcomes. This study aimed to investigate the potential mediating role of beliefs about the appropriateness of pain medicines for pain treatment on the association between pain catastrophizing and prescription opioid use in a community chronic non-cancer pain (CNCP) sample. Individuals (N = 420) diagnosed with CNCP participated in a cross-sectional online self-report study with validated measures of pain medication beliefs, pain catastrophizing, and current prescription opioid use. Two parallel multiple mediator analyses with percentile-based bootstrapping examined pathways to both prescription opioid use and high-dose use (≥ 100mg oral morphine equivalents/day), while controlling for pain intensity and other relevant covariates. Pain medication beliefs significantly mediated the association between pain catastrophizing and prescription opioid use (CI = 0.011, 0.033). A similar pattern of findings was found for high-dose opioid use, with pain medication beliefs significantly mediating the pain catastrophizing-high-dose use association (CI = 0.006, 0.050). Pain medication beliefs are a potentially modifiable psychological mechanism by which pain catastrophizing is associated with opioid use, including high-dose use. These findings have important implications for personalizing prevention and treatment programs.

Abstract
Background: The COVID-19 pandemic has forced sweeping social and behavioral changes that have adversely affected the general population. Many changes, such as business closures, working from home, increased psychological distress, and delayed access to health care, could have unique adverse effects on patients diagnosed with chronic pain (CP). The present study sought to examine perceived changes in the CP experience brought about by the COVID-19 pandemic.

Design: Participants included 487 self-reported patients with musculoskeletal, neuropathic, or postsurgical pain recruited using CloudResearch. A 53-item survey was created to assess changes in perceived pain, mood, control over pain, physical activity, employment, and medical access since the onset of the pandemic.

Results: Results suggested a worsening of the pain experience, particularly for women, with greater pain, negative affect, sedentary functioning, perceived decline in treatment quality, and increased treatment delays. Of note, pandemic-related declines in control over pain, which represents an important clinical target, are associated with other pandemic-related declines and also mediates relevant associations.

Conclusions: For frontline treatment providers, particularly primary care nurses and physicians, these findings may be relevant in order to reduce the likelihood of a worsening of symptoms, loss of self-efficacy regarding management of pain and/or potential maladaptive increase in the use of pain medications.

Topical lidocaine is widely used in current practice for a variety of pain conditions. This literature review shows that its limited absorption and relative lack of systemic adverse events are an attractive analgesic option for a number of vulnerable patients. Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis. Topical lidocaine may be a great alternative alone or in addition to systemic drugs and non-pharmacological approaches for an optimized pain management and in multimodal analgesia.

Background: While preoperative gabapentinoids are commonly used in surgical multimodal analgesia protocols, little is known regarding the effects this therapy has on prolonged postsurgical opioid use. In this observational study, we used data from a large integrated health care system to estimate the association between preoperative day-of-surgery gabapentinoids and the risk of prolonged postsurgical opioid use.

Methods: We identified adults age ≥65 years undergoing major therapeutic surgical procedures from a large integrated health care system from 2016 to 2019. Exposure to preoperative gabapentinoids on the day of surgery was measured using inpatient medication administration records, and the outcome of prolonged opioid use was measured using outpatient medication orders. We used stabilized inverse probability of treatment-weighted log-binomial regression to estimate risk ratios and 95% confidence intervals (CIs) of prolonged opioid use, comparing patients who received preoperative gabapentinoids to those who did not and adjusting for relevant clinical factors. The main analysis was conducted in the overall surgical population, and a secondary analysis was conducted among procedures where at least 30% of all patients received a preoperative gabapentinoid.

Results: Overall, 13,958 surgical patients met inclusion criteria, of whom 21.0% received preoperative gabapentinoids. The observed 90-day risk of prolonged opioid use following surgery was 0.91% (95% CI, 0.77-1.08). Preoperative gabapentinoid administration was not associated with a reduced risk of prolonged opioid use in the main analysis conducted in a broad surgical population (adjusted risk ratio [adjRR], 1.19 [95% CI, 0.67-2.12]) or in the secondary analysis conducted in patients undergoing colorectal resection, hip arthroplasty, knee arthroplasty, or hysterectomy (adjRR, 1.01 [95% CI, 0.30-3.33]).

Conclusions: In a large integrated health system, we did not find evidence that preoperative gabapentinoids were associated with reduced risk of prolonged opioid use in patients undergoing a broad range of surgeries.

Chronic pain (CP) and opioid use disorders (OUD) are highly prevalent, costly health problems that are best treated with an interprofessional biopsychosocial approach [1, 2]. Patients might not disclose their substance use because of stigma, fear of legal repercussions, inaccessible treatment resources, or other factors [3]. Similarly, CP might be dismissed as irrelevant, or it might be left unaddressed because of stigma and limited accessible treatment options [4]. People with either condition might be labeled as “drug-seeking,” which adds bias that precludes the patient-centered approach needed to best care for them [5]. Our team of providers, nurses, and a pharmacist with expertise in CP and OUD developed a blended educational program to help professionals in an emergency department observation unit (EDOU) better understand and treat this population.

Objective: The aim of this study was to conduct a systematic review and network meta-analysis of all randomized trials investigating effect of anti-calcitonin gene-related peptide monoclonal antibodies on disability related to migraine in adult patients.

Materials and methods: Medline, Embase, and Cochrane Central Register of Controlled Trials searched from inception to July 2020 with an additional review of clinical trial registries. Disability evaluated using change in patient reported Migraine Disability Assessment scores from baseline were considered for the final analysis. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects.

Results: Overall 41 studies (7095 migraineurs in 9 randomized trials) were included with treatment course of at least 12 weeks. Subcutaneous injections of fremanezumab 675+225+225 mg QM and 225+225+225 mg QM were more effective in reducing disability in chronic and episodic migraine patients, respectively, with higher median difference in Migraine Disability Assessment score from baseline compared with other treatments including erenumab (70 mg QM; 140 mg QM), galcanezumab (120 mg QM; 240 mg QM), and low doses of fremanezumab (225 mg single dose; 675 mg single dose).

Discussion: For short-term prevention of migraine, fremanezumab demonstrated slightly better improvement in disability compared with other anti-calcitonin gene-related peptide monoclonal antibodies in adult patients with migraine.

Study objective: We aimed to assess and compare the analgesic efficacies and adverse effects of ketamine administered through a breath-actuated nebulizer at 3 different dosing regimens for emergency department patients presenting with acute and chronic painful conditions.
Methods: This was a prospective, randomized, double-blinded trial comparing 3 doses of nebulized ketamine (0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg) administered through breath-actuated nebulizer in adult emergency department patients aged 18 years and older with moderate to severe acute and chronic pain. The primary outcome included the difference in pain scores on an 11-point numeric rating scale between all 3 groups at 30 minutes. Secondary outcomes included the need for rescue analgesia (additional doses of nebulized ketamine or intravenous morphine) and adverse events in each group at 30 and 60 minutes.
Results: We enrolled 120 subjects (40 per group). The difference in mean pain scores at 30 minutes between the 0.75 mg/kg and 1 mg/kg groups was 0.25 (95% confidence interval [CI] 1.28 to 1.78); between the 1 mg/kg and 1.5 mg/kg groups was -0.225 (95% CI -1.76 to 1.31); and between the 0.75 mg/kg and 1.5 mg/kg groups was 0.025 (95% CI -1.51 to 1.56). No clinically concerning changes in vital signs occurred. No serious adverse events occurred in any of the groups.
Conclusion: We found no difference between all 3 doses of ketamine administered through breath-actuated nebulizer for short-term treatment of moderate to severe pain in the emergency department.

Abstract
Background: Few studies have evaluated patterns of systemic opioid use among patients initiating spinal cord stimulation therapy for chronic pain. This study evaluated systemic opioid discontinuation and/or dose reduction and total health care cost after the start of spinal cord stimulation therapy.

Methods: Using a commercial insurance claims database (2008-2017), we analyzed opioid utilization patterns in patients initiating spinal cord stimulation therapy over a 1-year baseline and 2-year follow-up. The primary end point was defined as either discontinuation (≥365-day gap between prescription fills or total days' supply in follow-up ≤30 days) or ≥50% reduction in average daily morphine milligram equivalent dose. "Costs" were defined as total payer plus patient out-of-pocket payments.

Results: A total of 5,878 patients met the selection criteria. Of these, 152 (2.6%) showed no opioid prescription data at any point in the study period. Among patients with one or more prescriptions, 42.0% met the primary end point (22.0% discontinued, and 20.0% reduced their dose by 50% or more). Mean total adjusted costs were significantly reduced in years 1 and 2 of follow-up relative to baseline (excluding device insertion costs). The average time to breakeven when accounting for device trial and permanent insertion cost was 3.1 years among those who met the composite end point and 4.2 years among those who did not.

Conclusions: This analysis shows that among patients who continued spinal cord stimulation therapy for at least 2 years, a significant proportion were able to reduce and/or discontinue systemic opioid use, with costs after the start of therapy significantly reduced relative to baseline.

Abstract
Background: Pain medicine fellowship applicants often seek information about programs from the Internet, which is becoming even more relevant with the transition to virtual interviews as a consequence of the global pandemic. Previous literature has revealed the significance of training program websites as part of the application process in other specialties.

Objectives: The objective of this cross-sectional study was to evaluate the content, design, organization, and user friendliness by using a composite score to determine the quality of the pain medicine fellowship websites (PMFW).

Methods: Accredited pain medicine fellowship programs was queried from three databases for pain medicine education: (1) Electronic Residency Application Service (ERAS); (2) the Fellowship and Residency Electronic Interactive Database (FREIDA); and (3) the National Resident Matching Program (NRMP). Programs that appeared within one and/or more databases were eligible for study inclusion. PMFW were evaluated for the accessibility of recruitment and education content items. The quality of PMFW was determined as multifactorial composed of four dimensions: content, design, organization, and user friendliness.

Results: For program recruitment, PMFW contained an average of 12 ± 4.0 of 32 content items (38%) for fellowship programs: (1) 83% of fellowship programs specified the number of positions available for the 2021 Match; (2) 17% indicated alumni career placement; (3) 6.8% supplied interview dates; and (4) merely 4.9% detailed the selection process. For program education, PMFW contained an average of 7 ± 3.4 of 16 content items (44%): (1) 70% of programs provided a rotation schedule; (2) 49% detailed operative experiences; and (3) just 16% included simulation training. Regarding the quality based on content, design, organization, and user friendliness, the average PMFW was not "good" with only 1% of PMFW meeting "great" standards. A kappa value of 0.92 was calculated for inter-rater reliability.

Conclusions: The web presence of pain medicine fellowship programs falls short of providing essential accessibility, content, design, organization, and user friendliness to allow applicants to adequately access information about program characteristics. There are ample opportunities to increase the effectiveness of PMFW to benefit training programs and to inform prospective applicants, especially given the rise of virtual applications and interviews.