Acute pain: Journals & articles

Abstract
Many patients experience acute pain, which has been associated with numerous negative consequences. Pain education has been proposed as a strategy to improve acute pain management. However, studies report limited effects with educational interventions for acute pain in adults, which can be explained by the underuse of the person-centered approach. Thus, we aimed to systematically review and synthetize current evidence from quantitative, qualitative and mixed-methods studies describing patients' needs and preferences for acute pain education in adults. We searched original studies and gray literature in 7 databases, from January 1990 to October 2023. Methodological quality was assessed with the Mixed Methods Appraisal Tool. A total of 32 studies were included (n = 1847 patients), two-thirds of which were qualitative studies of high methodological quality. Most of the studies were conducted over the last 15 years in patients with postsurgical and posttraumatic pain, identified as White, with a low level of education. Patients expressed the greatest need for education when it came to what to expect in pain intensity and duration, as well how to take the medication and its associated adverse effects. The most frequently reported educational preferences were for in-person education while involving caregivers and to obtain information first from physicians, then by other professionals. This review has highlighted the needs and preferences to be considered in pain education interventions, which should be embedded in an approach cultivating communication and partnership with patients and their caregivers. The results still need to be confirmed with different patient populations.

Abstract
Purpose of review: Acute facial pain presents a complex challenge in medical practice, requiring a comprehensive and interdisciplinary approach to its management. This narrative review explores the contemporary landscape of treating acute facial pain, delving into pharmacological, non-pharmacological, and advanced interventions. The significance of tailored treatment strategies, rooted in the diverse etiologies of facial pain, such as dental infections, trigeminal neuralgia, temporomandibular joint disorders, sinusitis, or neurological conditions like migraines or cluster headaches, is underscored. We particularly emphasize recent advances in treating trigeminal neuralgia, elucidating current treatment concepts in managing this particular acute facial pain.

Recent findings: Recent research sheds light on various treatment modalities for acute facial pain. Pharmacotherapy ranges from traditional NSAIDs and analgesics to anticonvulsants and antidepressants. Non-pharmacological interventions, including physical therapy and psychological approaches, play pivotal roles. Advanced interventions, such as nerve blocks and surgical procedures, are considered in cases of treatment resistance. Moreover, we explore innovative technologies like neuromodulation techniques and personalized medicine, offering promising avenues for optimizing treatment outcomes in acute facial pain management. Modern management of acute facial pain requires a nuanced and patient-centric approach. Tailoring treatment strategies to the individual's underlying condition is paramount. While pharmacotherapy remains a cornerstone, the integration of non-pharmacological interventions is essential for comprehensive care. Advanced interventions should be reserved for cases where conservative measures prove inadequate. Furthermore, leveraging innovative technologies and personalized medicine holds promise for enhancing treatment efficacy. Ultimately, a holistic approach that considers the diverse needs of patients is crucial for effectively addressing acute facial pain.

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
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
Objectives: Understanding adolescent perspectives on prescribed opioids in the context of medical care for acute pain is needed to prevent opioid-related adverse outcomes. We explored factors that may influence opioid decision-making and use behaviors among adolescents prescribed opioids for acute pain.

Methods: We conducted semi-structured interviews with nineteen adolescents (63% females, ages 12-17) prescribed opioids upon discharge from surgery or intensive care unit admission. Interview transcripts were coded using inductive thematic analysis.

Results: Five themes were identified: "Opioid use to reduce extreme pain and facilitate acute recovery"; "Familiarity with risks and negative effects of opioids"; "Assessment of opioid risk based on individual characteristics and use behaviors"; "Careful balance of risks, benefits, and symptoms when taking opioids"; "Importance of trusted adults for adolescent opioid management". Adolescents commonly believed opioids are only appropriate for severe pain that cannot be managed with other strategies. Most (but not all) adolescents were aware of addiction and other potential opioid harms, and generally disapproved of misuse. However, a few adolescents would consider taking unprescribed opioids for severe pain. Adolescents wanted to be well informed for opioid decision-making, considering guidance from trusted adults.

Discussion: Adolescents often demonstrated active and sound participation in shared opioid decision-making, influenced by complex integration of inputs and self-reflection. Conversely, potential factors that could contribute to risky behaviors included low personal risk perceptions, uncertainty about what constitutes opioid misuse, and avoidance of prescribed opioids despite extreme pain. Future studies may explore associations of adolescents' opioid decision-making with longer-term pain and opioid-related outcomes.

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
The molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex-differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry (MS). MS spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at three months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement or coagulation responses. This data provides preliminary evidence that biological processes during an acute LBP episode may contribute to resolution, or persistence, of LBP symptoms at three months, however, these processes differ between males and females. PERSPECTIVE: Differential expression of serum proteins was observed between male and female participants during an acute LBP episode. This preliminary work provides a foundation for future research targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP.

Abstract
There is general agreement that acute pain management is an important component of perioperative medicine. However, there is no consensus on the best model of care for perioperative pain management, mainly because evidence is missing in many aspects. Comparing the similarities and differences between countries might reveal some insights into different organisational models and how they work. Here, we performed a narrative review to describe and compare the structures, processes and outcomes of perioperative pain management in the healthcare systems of four European countries using Donabedian's framework as a guide. Our comparison revealed many similarities, differences and gaps. Different structures of acute pain services in the four countries with no common definition and standards of care were found. Protocols have been implemented in all countries and guidelines in some. If outcome is assessed, it is mainly pain intensity, and many patients experiencing more intense pain than others have common risk factors (e.g. preoperative pain, preoperative opioid intake, female sex and young age). Outcome assessment beyond pain intensity (such as pain-related physical function, which is important for early rehabilitation and recovery) is currently not well implemented. Developing common quality indicators, a European guideline for perioperative pain management (e.g. for patients at high risk for experiencing severe pain and other outcome parameters) and common criteria for acute pain services might pave the way forward for improving acute pain management in Europe. Finally, the education of general and specialist staff should be aligned in Europe, for example, by using the curricula of European Pain Federation (EFIC).

Abstract
Purpose: The study aims to compare the analgesic efficacy of two analgesic interventions, continuous paravertebral (PVB) nerve block alone with continuous paravertebral and intercostal nerve block (PVB/ICB) in patients undergoing thoracotomy.

Methods: A total of 70 patients undergoing thoracotomy were randomly enrolled in either continuous paravertebral nerve block (PVB) group or in continuous paravertebral and intercostal nerve block (PVB/ICB) group and received corresponding blocks. Analgesic efficacy measured by Visual Analog Scale (VAS) pain score, hemodynamic effects, total narcotic consumption, sedation score, patient's length of stay in hospital and patient's satisfaction with the analgesic technique were recorded.

Results: Demographic characteristics of the patients were similar in both groups. The mean VAS pain score was not statistically significant in both groups at 24 h. The mean pulse rate and blood pressures were comparable in both groups for the first 24 h. Nalbuphine consumption was significantly higher in PVB group as compared to PVB/ICB group at 1 h (p = 0.01), 6 h (p = 0.03) and 12 h (p = 0.009) and 24 h (p = 0.03). The mean total nalbuphine consumption in the PVB group was higher (28.29 mg vs. 22.63 mg) and statistically significant then PVB/ICB group (p = 0.03). The total tramadol consumption as a rescue analgesic was higher in the PVB group (131.42 mg) as compared to PVB/ICB group (120 mg) after 24 h but not statistically significant (p = 0.17).

Conclusion: Continuous paravertebral nerve block with intercostal nerve block provides effective post-operative pain relief after thoracotomy with reduced narcotic consumption compared to continuous paravertebral nerve block alone.

Keywords: Acute pain; Analgesics; Bupivacaine; Nalbuphine; Nerve block; Opioid; Pain; Thoracotomy; Tramadol.

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
Objective: Transforaminal epidural steroid injections (TESIs) are widely administered for sciatica. The aim of this trial was to evaluate the effectiveness of TESIs in patients with acute sciatica (<8 wk).

Methods: This study was conducted in two Dutch hospitals. Participants (n=141) were randomly assigned to: 1) usual care and TESI of 1ml of 40mg/ml Methylprednisolone plus 1ml of 0.5% Levobupivacaine (intervention 1); 2) usual care and transforaminal epidural injection with 1 ml of 0.5% Levobupivacaine and 1ml NaCl 0.9% (intervention 2); 3) usual care consisting of oral pain medication with or without physiotherapy (control). Co-primary outcomes were back- and leg pain intensity, physical functioning and recovery measured during 6-month follow-up.

Results: There were no significant mean differences in co-primary outcomes between groups during follow-up, except for leg pain when comparing intervention group 1 with control (-0.96 95%CI:-1.83 to -0.09). For secondary outcomes, some significant between group differences were found for treatment satisfaction and surgery, but only when comparing intervention group 2 to control. Post-hoc analyses showed a significant difference in response (50% improvement of leg pain [yes/no]) between intervention 1 and the control group at 3 months and that both intervention groups used less opioids.

Discussion: Except for a statistically significanteffect of TESI on leg pain for patients with acute sciatica compared to usual care, there were no differences in co-primary outcomes. Nonetheless, transforaminal epidural injections seem to be associated with less opioid use, which warrants further exploration.

Abstract
Background: To investigate the effects of body mass index (BMI) on intensity postoperative pain in patients who underwent thoracic paravertebral block (TPVB) for postoperative analgesia after video-assissted thoracoscopic surgery (VATS).

Methods: Patients aged 18-80 years, ASA I-III, and BMI 18-40 kg/m2 who underwent elective VATS were included in the study. The patients were divided into 3 groups according to their BMI levels. TPVB was performed under ultrasound-guidance at the fifth thoracic vertebrae, and 30 ml of 0.25% bupivacaine was injected. The patient-controlled analgesia (PCA) was performed by using morphine and multimodal analgesia was performed. As a rescue analgesic agent, 0.5 mg/kg tramadol was given to patients intravenously when a score of visual analog scale (VAS) at rest was ≥ 4. The primary outcome was determined as VAS scores at rest and cough. Secondary outcomes were determined as postoperative morphine consumption, additional analgesic requirement, and side effects.

Results: The post-hoc test revealed that the VAS resting scores at the 4th hour (p: 0.007), 12th hour (p: 0.014), and 48th hour (p: 0.002) were statistically significantly lower in Group I compared to Group II. Additionally, VAS resting scores were also statistically significantly lower in Group I compared to Group III at all time points (p < 0.05). Similarly, the post-hoc test indicated that the VAS coughing scores at the 4th hour (p: 0.023), 12th hour (p: 0.011), and 48th hour (p: 0.019) were statistically significantly lower in Group I compared to Group II. Moreover, VAS coughing scores were statistically significantly lower in Group I compared to Group III at all time points (p < 0.001). Furthermore, there were statistically significant differences in terms of additional analgesic use between the groups (p: 0.001). Additionally, there was a statistically significant difference in terms of morphine consumption via PCA and morphine milligram equivalent consumption between the groups (p < 0.001).

Conclusions: Higher postoperative VAS scores with TPVB applied in obese patients and the consequent increase in additional analgesics and complications require more specific postoperative management in this patient group.

Keywords: Acute pain; Body mass index; Paravertebral block; Patient-controlled analgesia; Postoperative analgesia; Video-assissted thoracoscopic surgery.

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
Objectives: Acute postoperative pain (APP) is the main cause of postoperative dissatisfaction; however, traditional methods of pain assessment provide limited insights into the dynamics and development of APP. This study used the experience sampling method (ESM) to understand the dynamics of APP over time in relation to various patient factors.

Methods: Forty patients scheduled to undergo total knee replacement surgery were recruited in this study. Following an initial assessment, a short report questionnaire was sent to the patients via 10 digital alerts per day to assess the pain levels during two preoperative and the first 6 postoperative days. The data were analyzed using multilevel regression including random intercept and slope.

Abstract
Background: Opioid analgesics are commonly used for acute low back pain and neck pain, but supporting efficacy data are scarce. We aimed to investigate the efficacy and safety of a judicious short course of an opioid analgesic for acute low back pain and neck pain.

Methods: OPAL was a triple-blinded, placebo-controlled randomised trial that recruited adults (aged ≥18 years) presenting to one of 157 primary care or emergency department sites in Sydney, NSW, Australia, with 12 weeks or less of low back or neck pain (or both) of at least moderate pain severity. Participants were randomly assigned (1:1) using statistician-generated randomly permuted blocks to guideline-recommended care plus an opioid (oxycodone-naloxone, up to 20 mg oxycodone per day orally) or guideline-recommended care and an identical placebo, for up to 6 weeks. The primary outcome was pain severity at 6 weeks measured with the pain severity subscale of the Brief Pain Inventory (10-point scale), analysed in all eligible participants who provided at least one post-randomisation pain score, by use of a repeated measures linear mixed model. Safety was analysed in all randomly assigned eligible participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000775516).

Keywords: acute pain; chronic kidney failure pain management; continuous catheter analgesia; erector spinae plane (esp) blockade; opioid-free analgesia; perioperative analgesia; regional anaesthesiology; transplant

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

Keywords: Chronic headache; Cortical spreading depression; Microglia; Migraine; Neuroinflammation.

Acute pain; Advanced pain procedure; Cancer; Chronic pain; Disparities; Diversity; Elderly; Ethnicity; Gender; Geography; Obstetric; Pediatric; Race; Rural; Socioeconomic; Veteran.

Keywords: Acute pain; Multimodal pain control; Naltrexone; Opioids; Post-surgical pain.

Keywords: Analgesia; Emergency department; Pre-hospital; Sufentanil; Systematic review.

Keywords: Adverse Drug Event; Analgesics; Burns; Opioid; Pain.

Keywords: Acute pain; Patient satisfaction; Patient-centred care; Shared decision-making.

Keywords: Erector spinae plane block; Postoperative pain; Thoracoscopic lobectomy.

Keywords: Acute Pain; Anesthesia, Local; Pain Management.

Keywords: High-sensitivity cardiac troponin; chest pain; emergency department; outcomes; cardic troponin.

Background: This prospective, open-label trial was conducted to fulfil a post-approval commitment made to the competent authorities to extend the indication of the strong opioid analgesic tapentadol hydrochloride oral solution (OS) to the pediatric population.

Patients and methods: The trial assessed the pharmacokinetic (PK) profile of tapentadol, tapentadol-O-glucuronide and tapentadol-O-sulfate after administration of multiple doses of tapentadol OS (1.25 mg tapentadol/kg bodyweight every 4 h for up to 72 h) in children aged 2 to <7 years after a painful event that produces acute pain requiring treatment with a strong analgesic. The obtained PK data were integrated into a previously developed population PK (popPK) model based on single-dose data and then a model-based PK evaluation was performed. The primary trial endpoint was the area under the concentration-time curve at steady state for the dosing interval (AUCτ,ss) for tapentadol.

Results: Ten children received tapentadol OS; all completed the trial. Multiple administrations of the trial medication resulted in tapentadol serum concentrations within the concentration range predicted by the previously developed popPK model. The estimated model-based AUCτ,ss values for tapentadol ranged from 142 to 321 h•ng/mL. They were within the predicted exposure range with no higher than expected accumulation for the employed dosing regimen and also within the targeted steady state exposure range observed in adults receiving multiple doses of immediate release tapentadol 50 to 100 mg. The treatment regimen was safe and well tolerated.

Conclusion: The findings confirm the linear and predictable PK profile of tapentadol hydrochloride. The good agreement between the observed data and the model predictions shows the value of modelling and simulations in the planning and analysis of pediatric clinical trials and the ability to utilize the established PK models to predict multiple dose exposure.

Objectives: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials.

Methods: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo.

Results: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea.

Conclusions: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

Abstract
RATIONALE AND SCOPE OF THE GUIDELINES Pain is a subjective unpleasant sensory and emotional experience. Acute pain occurs irrespective of age and has a prevalence of about 5% of the general population. Surgical procedures and painful diagnostic procedures are the main causes of this unpleasant and dangerous phenomenon for hospitalized children. It should be remembered that maintaining homeostasis in a child undergoing surgery is also affected by provision of an adequate level of analgesia and sedation as well as nerve conduction block within the surgical site. Even though both paediatric anaesthesiologists and paediatric surgeons know that the therapeutic activities during the perioperative period should be focused on ensuring sufficient analgesia and haemodynamic stability in surgical patients, as many as 70% of children undergoing surgery may experience moderate to severe pain [1-7]. Moreover, pain management is one of the fundamental human rights, i.e. the right to relief of suffering. According to the declaration of the 13th World Congress on Pain in Montreal (September 2010), this right also includes children [8, 9]. In Poland, the law was amended in 2017, and now each patient is guaranteed the right to relief and treatment of pain (Journal of Laws of 2017, item 836). Unfortunately, this right is not always respected in paediatric patients. Many factors contribute to ineffective analgesia in paediatric patients, mainly insufficient knowledge and lack of experience (concerning the use of opioids in particular), as well as lack of management standards, the negative attitude of the personnel or poor organization [10-13]. In hospitals which, as a result of organizational changes, have implemented analgesic treatment regimens and regularly educate their personnel in these issues, both efficiency and effectiveness of pain relief in children are high [14]. For many years, Polish paediatric anaesthesio-logists have been promoting and streamlining the analgesic management of children, which has led to the development of the present publication. The regimens presented in it are based on both the latest medical reports and many years of the authors' experience. The classes of recommendations and levels of evidence have been prepared (Tables 1 and 2, respectively). The presented recommendations were formulated based on a survey of medical reports published in the last two decades.

Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. Twenty healthy volunteers were included in this randomized, placebo-controlled, double-blinded, crossover study assessing pain intensities (using numeric rating scale), secondary hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a well-established acute pain model with intradermal electrical stimulation. The authors compared the effect of 800-mg orally administered CBD on pain compared with placebo. They further examined the effect on hyperalgesia and allodynia. Cannabidiol whole blood levels were also measured. Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.

Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. Twenty-four healthy participants were included in this randomized, double-blinded, crossover study and received either a 1600-mg single-dose oral cannabidiol or placebo. Hyperalgesia, allodynia, and pain were induced by intracutaneous electrical stimulation. To provoke OIH, participants recieved an infusion of 0.1 µg/kg/min remifentanil over a time frame of 30 minutes, starting 100 minutes after oral cannabidiol ingestion. The primary outcome was the area of hyperalgesia (in square centimetres) up to 60 minutes after remifentanil administration. The area of allodynia (in square centimetres) and pain (numeric rating scale) were also assessed.Cannabidiol had no significant effect on hyperalgesia, allodynia, or pain at any time point of measurement compared with placebo. The area of hyperalgesia after remifentanil administration significantly increased compared with baseline (17.0 cm2 [8.1-28.7] vs 25.3 cm2 [15.1-39.6]; P = 0.013). Mean cannabidiol blood levels were 4.1 ± 3.0 µg/L (mean ± SD) at 130 minutes after ingestion and were 8.2 μg/L ± 6.9 µg/L (mean ± SD) at 200 minutes. Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.

Recent sham-controlled studies suggest placebo effects contribute to acute pain relief following mindfulness interventions. However, the specific effects of mindfulness processes and their interaction with placebo effects remain unclear. This study aimed to characterize the role of mindfulness and placebo processes underlying mindfulness-based pain attenuation. Both treatment (focused-attention mindfulness vs sham) and instruction ("told mindfulness" vs "told sham") were manipulated in a balanced placebo design. Changes in acute heat pain were evaluated in 153 healthy adults randomized to receive 6 x 20 minutes of one of the four treatment by instruction interventions or no treatment. Participants receiving any intervention demonstrated improved pain outcomes (unpleasantness, intensity and tolerance) relative to no treatment. The instruction manipulation increased expectation for pain relief in those told mindfulness relative to told sham, but there were no main effects or interactions of treatment or instruction on pain outcomes. However, irrespective of actual intervention received, the belief of receiving mindfulness predicted increased pain threshold and tolerance, with expectancy fully mediating the effect on pain tolerance. These findings suggest a lack of specific effects of mindfulness and instruction on acute pain. Nonetheless, participants' expectancies and beliefs about the treatment they received did predict pain relief. Together with the overall improvement following any intervention, these findings suggest that expectancy and belief may play a stronger role in attenuating acute pain in novices following brief mindfulness interventions than the actual mindfulness-specific processes or instructions delivered.

Purpose: Ketamine is a N-methyl-D-aspartate (NMDA) antagonist with strong analgesic properties. Its addition to the treatment of neuropathic pain may reduce pain intensity and improve overall quality of life. A systematic review and meta-analysis of randomized controlled trials was performed to investigate the addition of ketamine to the treatment of patients with neuropathic pain.

Patients and methods: GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to rate the overall certainty of the evidence for each outcome. Eighteen (18) randomized controlled trials including 706 participants were included for further analysis.

Results: Ketamine addition to standard treatment of neuropathic pain (NP) resulted in a statistically significant reduction of pain intensity at one week after the end of treatment with ketamine (MD -2.14, 95% CI -2.65 to -1.63; p<0.00001) and after 30 days after the end of treatment with ketamine (MD -1.68, 95% CI -2.25 to -1.12; p<0.00001) and a statistically significant increase in discomfort (RR 4.06; 95% CI 1.18 to 13.95; p=0.03), and psychedelic effects (RR 4.94; 95% CI 2.76 to 8.84; p<0.00001).

Conclusion: There is a statistically significant pain reduction by adding ketamine to the treatment of chronic NP when compared to the standard treatment. However, such pain reduction comes at the expense of adverse outcomes, especially psychedelic effects related to the administration of ketamine. However, the overall quality of certainty of evidence is low due to the clinical heterogeneity among the intervention characteristics of the trials analyzed (different administration routes, dosing regimen, therapy durations, different clinical characteristics of the population investigated). Future large multi-centered trials are necessary to confirm or not the results of the present review.

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.

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.

An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings in the fields of pain research and the prevention and management of pain. Original research, reviews, symposium reports, hypothesis formation and commentaries are all considered for publication.

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.

Pain Medicine is dedicated to pain clinicians, educators, and researchers with an interest in pain from various medical specialties and related health disciplines. The journal reflects the rapid growth in pain science and practice, as well as the field's need for policy, ethical, and forensic commentary on pain and its management. It promotes the visibility and development of pain medicine as a worldwide interdisciplinary medical specialty within a collaborative, multidisciplinary pain field.

Pain Practice, the official journal of the World Institute of Pain, publishes international multidisciplinary articles on pain and analgesia that provide its readership with up-to-date research, evaluation methods, and techniques for pain management.