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Background: There is clear evidence demonstrating the benefits of physical activity (PA) on pain and overall health, however, PA is challenging for many individuals living with chronic pain. Even non-exercise specialists can (cost) effectively promote PA, but many health professionals report a number of barriers in providing guidance on PA, suggesting that it is not consistently promoted. This expert position paper summarizes the evidence and provides five recommendations for health professionals to assess, advise and support individuals living with any chronic pain condition with a long life expectancy in adopting and sustaining physically active lifestyles., Methods: This position paper was prepared by the 'On The Move' Task Force of the European Pain Federation EFIC. Final recommendations were endorsed by the European Pain Forum, Pain Alliance Europe and the Executive Board of EFIC., Results: We recommend that all health professionals (1) Take a history of the persons' PA levels, and put PA on the agenda, (2) Advise that PA is important and safe for individuals living with chronic pain, (3) Deliver a brief PA intervention and support individuals living with chronic pain in becoming physically active, (4) Discuss acceptable levels of PA-related soreness and pain and (5) Provide ongoing support in staying physically active., Significance: Physical activity is safe and offers several advantages, including general health benefits, low risk of side effects, low cost and not requiring access to healthcare. Adoption of these recommendations can improve the quality of care and life of individuals living with chronic pain and reduce their overall health risks., (© 2024 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Context: The prevalence of persistent pain among breast cancer survivors (BCS) is high, and it is unclear what distinguishes those with persistent pain from those without. Research suggests that differences in somatosensory function evaluated by quantitative sensory testing (QST) may be responsible., Objectives: This study aimed to describe somatosensory profiles in terms of hyper- and hypoesthesia in BCS with and without persistent pain using reference data from healthy controls. Second, QST parameters of BCS with and without pain were compared with those of healthy controls (i.e., a negative control group) and patients with fibromyalgia (i.e., a positive control group)., Methods: Participants (n = 128) were divided into four equal groups: healthy controls, BCS with persistent pain, BCS without persistent pain, and patients with fibromyalgia. Nine QST parameters were evaluated at the trunk and at a remote location. Somatosensory profiles were determined by Z-score transformation of QST data using normative data from healthy controls., Results: At the trunk, compared to healthy controls, BCS with persistent pain exhibited sensory aberrations across five out of seven QST parameters: pressure pain threshold, mechanical detection, and thermal thresholds. Pain-free BCS showed similar sensory aberrations across the four QST parameters compared to healthy controls: mechanical detection and thermal thresholds. Temporal summation and conditioned pain modulation were not significantly different between groups., Conclusion: BCS with persistent pain exert aberrations in peripheral processing of nociceptive signals, heightened facilitation of nociceptive signals, and higher psychosocial burden when compared to pain-free BCS, healthy controls, and patients with fibromyalgia., Significance: This study investigates the somatosensory function of breast cancer survivors with and without persistent pain using quantitative sensory testing and two control group (i.e., patients with fibromyalgia and healthy controls). Our results indicate somatosensory aberrations within the peripheral, but not central pathways in breast cancer survivors with persistent pain. Our findings contribute to a better understanding of the somatosensory mechanisms underlying persistent pain, which may inform future interventions to prevent the development of persistent pain, and improve treatment modalities., (© 2024 European Pain Federation ‐ EFIC ®.)

Introduction: Chronic back pain is one of the most prevalent conditions and has a large socio-economic impact. The lack of routine use of non-pharmacological options and issues associated with pharmacological treatments underscore high unmet needs in the treatment of back pain. Although blue light phototherapy has proven efficacy in dermatology, limited information is available about its use in back pain., Methods: In this proof-of-concept, randomized controlled trial, a pain relief patch (PRP) delivered blue light at the site of back pain for 30 min during five treatment sessions. The comparator device delivered green light for 5 s but was worn for 30 min. A follow-up visit took place after the last treatment. The primary objective was to demonstrate the superiority of treatment by PRP, compared to the control device, in reducing pain intensity at the end of the treatment period. The post-treatment visual analog scale (VAS) pain intensity score for each group was calculated across the five treatment sessions and compared to the baseline. Secondary objectives included the disability score (Roland-Morris Disability Questionnaire) and safety., Results: The full analysis set included 171 patients. A statistically significant reduction in pain intensity occurred after the use of PRP ( p  < 0.02), but the study did not meet its primary objective of a superiority trial aimed at demonstrating a 0.6 cm difference in favor of PRP on the VAS scale. There was no significant change in the disability scores. Subgroup analyses were performed to identify the treatment response by patient characteristics such as pain intensity at baseline and skin type. As expected, safety data showed erythema and skin discoloration in the PRP group but not in the control group., Discussion/conclusion: This trial had multiple limitations that need to be addressed in future research. Although the primary objective was not achieved, this proof-of-concept study provides important efficacy and safety data in relation to the use of blue light in the treatment of chronic back pain and key insights that may support further research on similar devices., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01528332., Competing Interests: All the authors, except GV who was a Philips employee at the time of the trial, have no relationship with Philips. GVB and IW are employed by Heat2Move. RB, BM, AD, and MÜ act as pain expert advisors for multiple pharmaceutical and device companies including Heat2Move. The author AD declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Baron, Morlion, Dahan, Überall, von Basum and Wild.)

Concomitant use of multiple drugs in most patients with cancer may result in drug-drug interactions (DDIs), potentially causing serious adverse effects. These patients often experience unrelieved cancer-related pain (CRP) during and after cancer treatment, which can lead to a reduced quality of life. Opioids can be used as part of a multimodal pain management strategy when non-opioid analgesics are not providing adequate pain relief, not tolerated, or are contraindicated. However, due to their narrow therapeutic window, opioids are more susceptible to adverse events when a DDI occurs. Clinically relevant DDIs with opioids are usually pharmacokinetic, mainly occurring via metabolism by cytochrome P450 (CYP). This article aims to provide an overview of potential DDIs with opioids often used in the treatment of moderate-to-severe CRP and commonly used anticancer drugs such as chemotherapeutics, tyrosine kinase inhibitors (TKIs), or biologics. A DDI-checker tool was used to contextualize the tool-informed DDI assessment outcomes with clinical implications and practice. The findings were compared to observations from a literature search conducted in Embase and PubMed to identify clinical evidence for these potential DDIs. The limited results mainly included case studies and retrospective reviews. Some potential DDIs on the DDI-checker were aligned with literature findings, while others were contradictory. In conclusion, while DDI-checkers are useful tools in identifying potential DDIs, it is necessary to incorporate literature verification and comprehensive clinical assessment of the patient before implementing tool-informed decisions in clinical practice., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Studies on the concurrent validity of clinically applicable testing protocols for conditioned pain modulation (CPM) and temporal summation of pain (TSP) in breast cancer survivors (BCS) with persistent pain are lacking., Objectives: This study investigated the concurrent validity of two bedside protocols for CPM and TSP in comparison to a respective reference protocol. The participants' preferences for bedside CPM and TSP protocols were assessed., Methods: Thirty BCS experiencing persistent pain were included in this study. Each participant underwent a reference test along with two bedside alternatives for assessing both TSP and CPM. For CPM, a cold pressor test (CPT) and blood pressure cuff (BPC) were used as conditioning stimulus. The test stimulus was elicited in parallel by pressure pain threshold after 45 and 90 s of conditioning at the lower limb. The CPM reference test consisted of parallel heat stimuli at the forearms using a two-thermode system. TSP was elicited using a von Frey monofilament (256 mN) and an algometer (98 kPa) at the affected site and opposite lower limb. The TSP reference test consisted of heat stimuli at the affected site and opposite lower limb. Participants' testing preference was examined using a purpose-designed questionnaire. Spearman's rank test examined the correlation between protocols., Results: The two bedside CPM protocols were strongly correlated ( r = 0.787-0.939, p < 0.005). A strong correlation was found between the BPC protocol and reference test using the relative effect magnitude ( r = 0.541-0.555, p < 0.005). The bedside TSP protocols were moderately correlated with each other only at the lower limb using absolute change scores ( r = 0.455, p = 0.012). No significant correlation was found between the bedside and reference TSP protocols., Conclusion: The significantly moderate to very strong correlations between the bedside protocols validate their interchangeability. Researchers and clinicians should be able to choose which bedside protocol they utilize; however, participants favored the use of a BPC and algometer for the evaluation of CPM and TSP, respectively., (© 2024 the author(s), published by De Gruyter.)

The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes., Competing Interests: Declaration of interests BM received consultation fees from Haleon, GSK, and Grünenthal, and honoraria from Haleon, GSK, Grünenthal, Krka, Mundipharma, and Viatris, is the past president of the European Pain Federation and program director of the Belgian Interuniversity Course in Pain Management. AC received payment for work as group tutor for the course in Clinimetrics (EpidM, Amsterdam, Netherlands). JN and the Vrije Universiteit Brussel received lecturing or teaching fees from various professional associations and educational organisations. EKo received royalties for textbook chapters from Liber and Studentlitteratur, payment for a lecture from Eli Lilly, and is a member of the scientific board of the Swedish Rheumatism Association. PH received travel support from the German Osteopathic Society, the Icelandic Physiotherapy Association, and the Finish Musculoskeletal Medicine Society. All other authors declared no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pain is one of the most prevalent and long-term adverse effects described by people who have undergone breast cancer surgery. Non-helpful perceptions and thoughts about pain may contribute to the transition of acute to persistent pain. Adding educational interventions to the current physical therapy program in this population may help to improve or prevent persistent pain. Pain neuroscience education (PNE) is a type of educational intervention that addresses the experience of pain in a broader sense by explaining pain not only from a biomedical perspective, but also from a psychological and social perspective. A double-blinded randomized controlled trial (EduCan trial) investigated whether PNE, in addition to a standard physiotherapy program immediately after surgery for breast cancer, was more effective on somatosensory functioning in the short (4 months postoperatively) and long term (18 months postoperatively), than providing a biomedical explanation for pain. Somatosensory functioning was evaluated using a self-reported questionnaire as well as a comprehensive quantitative sensory testing evaluation. The findings of this study revealed that adding six sessions of PNE to a standard physical therapy program (n = 184) did not result in a significantly different course of somatosensory functioning up to 18 months postoperatively as compared to biomedical pain education. These findings provide an interesting basis for future research into who should receive PNE after surgery for breast cancer (e.g., patient profiling or phenotyping) and how we can tailor it to the individual to increase its effectiveness., (© 2023 American Association for Anatomy.)

This paper discusses the growing problem of persisting pain after successful treatment of breast cancer and presents recommendations for improving pain-related outcomes for this group. We discuss the dominant treatment approach for persisting pain post-breast cancer treatment and draw contrasts with contemporary treatment approaches to persistent pain in non-cancer-related populations. We discuss modern application of the biopsychosocial model of pain and the notion of variable sensitivity within the pain system, moment by moment and over time. We present the implications of increasing sensitivity over time for treatment selection and implementation. By drawing on transformative changes in treatment approaches to persistent non-cancer-related pain, we describe the potentially powerful role that an intervention called pain science education, which is now recommended in clinical guidelines for musculoskeletal pain, may play in improving pain and disability outcomes after successful breast cancer treatment. Finally, we present several research recommendations that centre around adaptation of the content and delivery models of contemporary pain science education, to the post-breast cancer context., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The aim of this study was to investigate the effect of pain neuroscience education compared to biomedical pain education after breast cancer surgery on (1) work status, (2) time until work resumption, and (3) change in return-to-work expectations up to 18 months post-surgery., Methods: Participants were randomly assigned to either pain neuroscience education (intervention group) or biomedical pain education (control group) in addition to a standard physical therapy program after surgery for breast cancer. The first four months following surgery, one to two physiotherapy sessions and three educational sessions were scheduled. After, two educational sessions and two physiotherapy sessions were held at six and eight months postoperatively. All outcomes were assessed at four, six, eight, 12 and 18 months postoperatively., Results: At 12 months, in the intervention group, 71% of the women returned to work compared to 53% in the control group (18% points difference, 95%CI:-0.1 to 35;p = 0.07). At 18 months, the differences decreased to 9% points, 95%CI:-26 to 7;p = 0.35). Neither time until work resumption (p = 0.46) nor change in estimation of own ability to return to work up to 18 months postoperatively (p = 0.21) significantly differed between both groups., Conclusion: No significant differences were found regarding return to work outcomes between women receiving pain neuroscience education versus biomedical pain education after breast cancer surgery. Further research is warranted to explore the potential role of pain neuroscience education in return-to-work interventions following breast cancer surgery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pain after breast cancer surgery is a common and disabling problem. A reliable and valid questionnaire to assess pain-related disability is the Pain Disability Index (0-70). However, properties of the Dutch version (PDI-DLV) have never been investigated in this population., Objective: To assess psychometric properties of the PDI-DLV after breast cancer surgery., Methods: For reliability, relative and absolute reliability were calculated with a one-week test-retest interval, as well as internal consistency. Moreover, content and construct validity were examined to evaluate validity., Results: One hundred twenty-three women were included. Relative reliability was good (intraclass correlation coefficient = 0.80). Standard error of measurement and minimal detectable change (absolute reliability) were 5.57 and 15.45 points, respectively. The mean difference between two measurements was -1.98 points, with 95% limits of agreement equal to 13.19 and -17.15. The within-subjects coefficient of variation was 59%. Internal consistency was confirmed (α = 0.87). The PDI-DLV was scored as understandable and complete (content validity). Construct validity was supported by confirmation of more than 75% of the tested hypotheses and of the one-factor model., Conclusion: The PDI-DLV is a valid questionnaire to assess pain-related disability 1 year after breast cancer surgery. Although absolute reliability is disputable, its good relative reliability allows evaluating changes between subjects.

Introduction: Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving management, possibly due to their complexity, and studies suggest that a simple setup of concise and behaviorally-orientated steps improves usability., Areas Covered: This article introduces the concept of opioid-induced constipation and provides an overview of existing guidelines in this field. We also propose simplified recommendations for managing opioid-induced constipation, derived from a synthesis of current guidelines and the principles of optimal guideline design theory., Expert Opinion: Despite standard treatment with laxatives and fluid intake in patients with opioid-induced constipation, escalation of treatment is often needed where μ-opioid receptor antagonists or newer medications such as lubiprostone, linaclotide, or prucalopride are used. Previous guidelines have not been used sufficiently and thus management of the condition is often insufficient. We therefore propose simplified recommendations to management, which we believe can come into broader use. It was validated in primary care for credibility, clarity, relevance, usability, and overall benefit. We believe that this initiative can lead to better management of the substantial proportion of patients suffering from side effects of opioids.

Abstract: Pain is one of the most common and long-lasting side effects reported by women surgically treated for breast cancer. Educational interventions may optimize the current physical therapy modalities for pain prevention or relief in this population. Pain neuroscience education (PNE) is an educational intervention that explains the pain experience not only from a biomedical perspective but also the psychological and social factors that contribute to it. Through a double-blinded randomized controlled trial (EduCan trial) it was investigated if PNE, in addition to the standard physiotherapy program immediately after breast cancer surgery, was more effective over the course of 18 months postoperatively than providing a biomedical explanation for pain. Primary outcome was the change in pain-related disability (Pain Disability Index, 0-70) over 12 months. Secondary outcomes included change in pain intensity, upper limb function, physical activity level, and emotional functioning over 4, 6, 8, 12, and 18 months postoperatively. Multivariate linear models for repeated (longitudinal) measures were used to compare changes. Preoperative and postoperative moderators of the change in pain-related disability were also explored. Of 184 participants randomized, the mean (SD) age in the PNE and biomedical education group was 55.4 (11.5) and 55.2 (11.4) years, respectively. The change in pain-related disability from baseline to 12 months postoperatively did not differ between the 2 groups (PNE 4.22 [95% confidence interval [CI]: 1.40-7.03], biomedical 5.53 [95% CI: 2.74-8.32], difference in change -1.31 [95% CI: -5.28 to 2.65], P = 0.516). Similar results were observed for all secondary outcomes. Future research should explore whether a more patient-tailored intervention would yield better results., (Copyright © 2023 International Association for the Study of Pain.)

Purpose: Pain and sensory disturbances are common side effects of breast cancer treatment. Differential somatosensory functioning may reflect distinct pathophysiological backgrounds and therapeutic needs. Aim was to examine whether questionnaires evaluating signs and symptoms related to somatosensory functioning correlate sufficiently with quantitative sensory testing (QST) in breast cancer survivors to warrant consideration for somatosensory profiling in clinical practice., Methods: One year after breast cancer surgery, 147 women underwent QST and completed following questionnaires: Douleur Neuropathique en 4 questions (DN4), Central Sensitization Inventory, Margolis Pain Diagram and Visual Analog Scales (VAS). Associations between the questionnaires and QST were evaluated using Spearman correlation coefficients (rs)., Results: Significant but weak ( r s < 0.30) correlations were found between total DN4 score and QST results at the inner upper arm for detection of sharp stimuli ( r s = 0.227), cold stimuli ( r s = -0.186), and painful heat stimuli ( r s = 0.179), as well as between QST evaluating conditioned pain modulation and the Margolis Pain Diagram on one hand ( r s = 0.176) and minimum-maximum pain intensity differences (VAS) on the other ( r s = -0.170)., Conclusion: Questionnaires evaluating signs and symptoms related to somatosensory functioning are insufficient for somatosensory profiling. Although somatosensory profiling may be valuable in a mechanism-based management, more research on the most appropriate clinical tools is needed.IMPLICATIONS FOR REHABILITATIONClinicians should be able to recognize that patients with persistent pain or sensory disturbances following breast cancer surgery may have a component of altered somatosensory processing as a significant contributor to their complaint in order to address it appropriately.Somatosensory profiling has yet to be implemented into clinical practice.No evidence-based recommendations can be made on the use of self-reported questionnaires to assess somatosensory processing in a breast cancer population based on the findings of this study.It is suggested to combine information on how individuals process and experience somatosensory stimulation with information from the patient interview or questionnaires to consider which biological, psychological and/or social factors may drive or sustain these neurophysiological processes.

Purpose: Here, we describe the development and pilot study of a personalized eHealth intervention containing a pain science education program and self-management support strategies regarding pain and pain-related functioning in female survivors of breast cancer. First, we aimed to evaluate the eHealth intervention's acceptability, comprehensibility, and satisfaction; second, we aimed to assess its preliminary efficacy., Methods: A mixed-method study design was used. Breast cancer survivors with persistent pain were recruited. After 6 weeks of engagement with the eHealth intervention, acceptability, comprehensibility, and satisfaction were measured quantitatively with a self-constructed questionnaire and described qualitatively using focus groups. A joint display was used to present the meta-interferences between data. Efficacy was assessed via mixed effects models with repeated measures (outcomes assessed at baseline, 6 weeks, and 12 weeks)., Results: Twenty-nine women with persistent pain after breast cancer surgery participated. Overall, the eHealth program was well received and experienced as easy to use and helpful. The eHealth intervention seems useful as an adjunct to comprehensive cancer aftercare. Efficacy estimates suggested a significant improvement in pain-related functioning, physical functioning, and quality of life., Conclusion: A personalized eHealth intervention appears valuable for persistent pain management after breast cancer surgery. A large controlled clinical trial to determine effectiveness, and a full process evaluation, seems warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The latest systematic review on the prevalence of pain in cancer survivors was published 5 years ago. The current review aims to provide an extended overview on the prevalence of pain, pain mechanisms, pain characteristics, and assessment methods in cancer survivors., Methods: A systematic research was conducted on 17th of April 2020 using MEDLINE, Embase, Scopus, Web of Science, and Cochrane looking at studies from 2014 to 2020. Studies had to report pain prevalence rates in cancer survivors with a solid tumor who finished curative treatment at least 3 months ago. Methodological quality was assessed by two independent reviewers using the Joanna Briggs Institute quality appraisal tool. Characteristics of the included studies, participants and reported pain prevalence rates were extracted. The reported prevalence rates of the individual studies were pooled within a meta-analysis. Meta-regressions were performed to identify possible determinants of the pooled pain prevalence., Results: After deduplication, 7300 articles were screened, after which 38 were included in the meta-analysis. Risk of bias was rated low in 26 articles and moderate in 12 articles. The pooled pain prevalence was 47% (95%CI 39-55), with a heterogeneity of 98.99%., Conclusion: This meta-analysis suggests that nearly half of cancer survivors report pain after completing curative treatment at least 3 months ago. However, substantial unexplained heterogeneity warrants cautious interpretation of these results. Meta-regression using cancer type, treatment location, pain measurement, and follow-up time as a covariate could not explain influencing factors explaining the high heterogeneity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective of this study was to investigate the impact of chronic low back pain (CLBP) on patients' personal and professional lives, and management strategies applied to treat CLBP., Methods: A 60-question survey was developed, and respondents from 16 countries with a self-reported physician's diagnosis of CLBP were recruited via an online market research survey panel. Respondents were stratified as having mild, moderate, or severe pain. Target sample sizes per country and for pain severity were set. Data were weighted according to the known population and prevalence of CLBP in each country and the number of respondents from that country., Results: Results from 9642 CLBP patients indicated that almost a quarter of patients with severe CLBP report a psychological comorbidity. Prescription pain medications were more commonly used by patients with severe CLBP (56%) than those with mild (20%) or moderate (34%) CLBP. Among those with severe CLBP who had been prescribed pain medication, 58% were prescribed opioids, with 1 in 4 patients using opioids for more than 5 years. Patients were primarily managed by general practitioners/primary care physicians, physiotherapists, neurologists, or orthopedic surgeons. CLBP negatively impacted patients' daily activities, social lives, and work productivity., Conclusion: Chronic low back pain has pronounced effects on patients' personal relationships, ability to work, and daily living. Almost 1 in four patients with severe CLBP reported a psychological comorbidity. Adherence to guidelines appears inconsistent, which is noteworthy as a substantial subgroup of patients with severe CLBP had been prescribed opioid medication for more than 5 years. Improved education is required to support healthcare professionals (HCPs) in identifying and understanding the complex biopsychosocial needs of CLBP patients to optimize pain management and to encourage referral of CLBP patients to physiotherapists and psychologists., (© 2022 Pfizer Inc. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Background & Aims: Opioids have a role in chronic pain management. However, opioid-induced constipation may cause patients to skip or reduce opioid doses, leading to inadequate pain relief and negatively impacting quality of life. We sought to establish a minimal clinically important difference to understand whether changes in quality of life scores are of value to patients., Methods: Integrated data from the double-blind, controlled, phase 3 COMPOSE-1 and COMPOSE-2 trials of naldemedine in chronic noncancer pain and opioid-induced constipation were used to determine minimal clinically important differences using Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Patients completed the questionnaires (5-point Likert scale; predose, Weeks 2, 4, and 12), kept a daily log of Bowel Movement and Constipation Assessment, and rated satisfaction at end of study. Minimal clinically important differences were computed using an anchor-based method with 6 anchors: 5 from the Bowel Movement and Constipation Assessment and 1 from patient satisfaction. Threshold values for each anchor were set to define responders versus nonresponders based on score definitions. Clinically meaningful cutoff values for changes in PAC-SYM and PAC-QOL scores were determined using receiver operating characteristic curves., Results: Data from 1095 patients (549, naldemedine; 546, placebo) were analyzed. The area under the curve for the receiver operating characteristic curves (ranges, 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) indicated that both instruments can discriminate responders and nonresponders for each anchor. PAC-SYM cutoff values ranged from -1.04 to -0.83; PAC-QOL cutoff values ranged from -0.93 to -0.82., Conclusions: Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic noncancer pain and opioid-induced constipation are clinically meaningful., Clinicaltrials: gov Registration: NCT01965158; NCT01993940., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To synthesize the evidence on the effectiveness of pain science education on pain, psychological factors and physical functioning in adults who underwent surgery., Data Sources: A systematic literature search of English articles using PubMed/Medline, Embase, Web of Science Core Collection, and Cochrane Library., Review Methods: The search strategy was constructed as follows: (((pain) AND (education)) OR (pain education)) AND (surgery). Only controlled quantitative studies in adults reporting outcome(s) on pain, psychological factors and/or physical functioning were included. Risk of bias was assessed using the Cochrane risk of bias tools. P -values and corresponding effect sizes for interaction-effect (time × group) portrayed the difference in change over time between groups were of interest. The last search was conducted on February 28, 2021., Results: Nine papers ( n  = 1078) were deemed eligible for this review. Two randomized controlled trials showed significant interaction effects. Breast cancer patients who had received one preoperative pain science education session showed a significant increase in postoperative pain compared to controls ( P -value = 0.0394). Furthermore, p sychological factors (pain catastrophizing and kinesiophobia) decreased in participants who had received pain science education before total knee arthroplasty, while this was not the case in the control group ( P -value < 0.001, ƞ2p:0.11)., Conclusions: Overall, pain science education did not result in any significant postoperative effects on pain, psychological factors and/or physical functioning compared to controls. There is currently no strong evidence for the implementation of pain science education in the perioperative period. Registration number: PROSPERO: ID 161267, registration number CRD42020161267.

Background: There is considerable public interest in whether Europe is facing an opioid crisis comparable to the one in the United States and the contribution of opioid prescriptions for pain to a potential opioid crisis., Methods: A task force of the European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug-related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioid-related harms over the last 20 years., Results: Data from 25 European countries were received. In most European countries opioid prescriptions increased from 2004 to 2016. The levels of opioid consumption and their increase differed between countries. Some Eastern European countries still have a low opioid consumption. Opioids are mainly prescribed for acute pain and chronic noncancer pain in some Western and Northern European countries. There was a parallel increase in opioid prescriptions and some proxies of opioid-related harms in France, Finland and the Netherlands, but not in Germany, Spain and Norway. In United Kingdom, opioid overdose deaths, but not opioid prescriptions increased between 2016 and 2018. There are no robust data available on whether prescribed opioids for pain patients contributed to opioid-related harms., Conclusions: There are marked differences between European countries in trends of opioid prescribing and of proxies for opioid-related harms. Europe as a whole is not facing an opioid crisis. Discussions on the potential harms of opioids should not obstruct their prescription for cancer pain and palliative care., Significance: Europe as a whole is not facing an opioid crisis. Some Eastern European countries have limited access to opioid medicines. Discussions on the potential harms of opioid medicines for noncancer pain should not obstruct opioid therapy for cancer therapy and palliative care., (© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Aim: We report the first patient roadmap in severe chronic low back pain (cLBP) in Europe, assessing the views of cLBP patients and general practitioners (GPs) who treat cLBP with regard to current cLBP management. Methodology: Patient journey mapping was conducted in four European countries to assess the views of cLBP patients (n = 20) and GPs (n = 40). Results: Four broad phases of cLBP, subdivided into eight individual steps, were identified as part of the patient journey, showing a disconnect between patients' and physicians' treatment goals, and expectations regarding pain relief levels for some patients. Conclusion: Improved communication, with greater involvement of patients in multimodal management decisions, might benefit the GP-patient relationship and overall outcomes for cLBP patients.

Objective: Opioid-induced constipation is among the most common side effects associated with opioid use in patients with chronic non-cancer pain, and it can have a significant negative impact on health-related quality of life (QOL). This analysis evaluated the effect of naldemedine 0.2 mg on patient-reported outcomes in three phase 3 clinical studies., Methods: COMPOSE-1 and COMPOSE-2 were identical randomized, double-blind, placebo-controlled, parallel-group studies of 12 weeks' duration, allowing data to be integrated (n=1095). COMPOSE-3 was similar in design, but of 52 weeks' duration (n=1241). Patients were adults with chronic non-cancer pain who had been treated with opioid analgesics for ≥3 months and experiencing opioid-induced constipation. Patient-reported outcomes included Patient Assessment of Constipation Symptoms (PAC-SYM; 12 questions assessed on a 5-point Likert scale), PAC-QOL (28 questions assessed on a 5-point Likert scale), and Subject Global Satisfaction (measured on a 7-point Likert scale). The proportion of patients achieving a ≥1.5 improvement in PAC-SYM and PAC-QOL was calculated. The correlation between change in PAC-SYM and PAC-QOL scores and frequency of bowel movements was also explored., Results: The proportion of PAC-SYM and PAC-QOL responders was significantly higher for naldemedine than for placebo at all assessed time points in COMPOSE-1/COMPOSE-2 (p<0.005 for both) and COMPOSE-3 (p<0.005 and p<0.0001, respectively). There was a statistically significant correlation between improvement in PAC-SYM/PAC-QOL and frequency of bowel movements at all time points (p≤0.0002). The majority of patients treated with naldemedine reported markedly or moderately improved satisfaction with constipation and abdominal symptoms on the Subject Global Satisfaction questionnaire., Discussion: Naldemedine treatment was associated with a rapid and sustained clinically relevant improvement in patient-reported outcomes, indicating improvement in opioid-induced constipation-related symptoms and QOL., Clinicaltrialsgov Registration: NCT01965158, NCT01993940, NCT01965652., Competing Interests: Michael Camilleri has provided scientific advice to Shionogi and has received a research grant from AstraZeneca in the field of opioid-induced constipation. Martin Hale was a clinical trial investigator, consultant to Shionogi Inc. and received a stipend for review of the clinical study report. Bart Morlion was a clinical trial site investigator for Shionogi Inc.; a consultant for Astellas Pharma Europe Ltd, Boehringer Ingelheim International, Boston Scientific, Bayer, Lilly, Reckitt Benckiser, Grünenthal, Mundipharma International, TEVA Pharmaceuticals Europe, GSK Consumer Healthcare, and Kyowa Kirin; and a speaker for Mundipharma International, Pfizer Inc, Shionogi Inc., Kyowa Kirin, and Procter and Gamble Company. Jan Tack has provided scientific advice to Allergan, Kyowa Kirin, Shionogi, and Shire, has been a speaker for Allergan and Kyowa Kirin, and has received a research grant from Kyowa Kirin related to opioid-induced constipation. Lynn Webster has provided scientific advice to Arbor Pharmaceuticals and BDSI; has worked on advisory boards for BDSI, Ensysce Biosciences, Neurana, and Salix; has received travel expenses from BDSI, Ensysce Biosciences, Elysium, Neurana, and Salix; has received personal fees for consultation from Bonti, Charleston Labs, Daiichi Sankyo, Depomed, Egalet, Elysium, Indivior, Insys Therapeutics, Inspirion Therapeutics, Kempharm, Mallinckrodt Pharmaceuticals, Merck, Pain Therapeutics, Pernix, Pfizer, Shionogi, Teva, Trevena, Trevi, and Vallon, outside the submitted work. James Wild received a stipend from Shionogi Inc. for review of the clinical study report. The authors report no other conflicts of interest in this work., (© 2021 Camilleri et al.)

Background: Opioid use for chronic non-cancer pain (CNCP) is under debate. In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC)., Methods: The clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed. Two categories of guidance are given: Evidence-based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case-series, case-control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) and formal multistep procedures to reach a set of consensus recommendations. The clinical practice recommendations were reviewed by five external reviewers from North America and Europe and were also posted for public comment., Results: The European Clinical Practice Recommendations give guidance for combination with other medications, the management of frequent (e.g. nausea, constipation) and rare (e.g. hyperalgesia) side effects, for special clinical populations (e.g. children and adolescents, pregnancy) and for special situations (e.g. liver cirrhosis)., Conclusion: If a trial with opioids for chronic noncancer pain is conducted, detailed knowledge and experience are needed to adapt the opioid treatment to a special patient group and/or clinical situation and to manage side effects effectively., Significance: If a trial with opioids for chronic noncancer pain is conducted, detailed knowledge and experience are needed to adapt the opioid treatment to a special patient group and/or clinical situation and to manage side effects effectively. A collaboration of medical specialties and of all health care professionals is needed for some special populations and clinical situations., (© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Background: Opioid use for chronic non-cancer pain (CNCP) is complex. In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC)., Methods: The clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed. Two categories of guidance are given: Evidence-based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case-series, case-control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) and formal multistep procedures to reach a set of consensus recommendations. The clinical practice recommendations were reviewed by five external reviewers from North America and Europe and were also posted for public comment., Results: The key clinical practice recommendations suggest: (a) first optimizing established non-pharmacological treatments and non-opioid analgesics and (b) considering opioid treatment if established non-pharmacological treatments or non-opioid analgesics are not effective and/or not tolerated and/or contraindicated. Evidence- and clinical consensus-based potential indications and contraindications for opioid treatment are presented. Eighteen GCP recommendations give guidance regarding clinical evaluation, as well as opioid treatment assessment, monitoring, continuation and discontinuation., Conclusions: Opioids remain a treatment option for some selected patients with CNCP under careful surveillance., Significance: In chronic pain, opioids are neither a universal cure nor a universally dangerous weapon. They should only be used for some selected chronic noncancer pain syndromes if established non-pharmacological and pharmacological treatment options have failed in supervised pain patients as part of a comprehensive, multi-modal, multi-disciplinary approach to treatment. In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients., (© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Background: Pain therapy in inpatients is regularly suboptimal and might be improved by clinical pharmacy services. In our hospital, we have implemented a software-supported 'Check of Medication Appropriateness' (CMA), which is a centralized pharmacist-led service consisting of a clinical rule-based screening for potentially inappropriate prescriptions (PIPs), and a subsequent medication review by pharmacists. We aimed to investigate the impact of the CMA on pain-related prescribing., Methods: A quasi-experimental study was performed in a large teaching hospital, using an interrupted time series design. Pre-implementation, patients were exposed to standard of care. Afterwards, a pain-focused CMA comprising 12 specific clinical rules pertaining to analgesic prescribing were implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of pain-related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the post-implementation period., Results: At baseline, a median number of 13.1 (range: 9.5-15.8) residual PIPs per day was observed. After the CMA intervention, the number was reduced to 2.2 (range: 0-9.5) per day. Clinical rules showed an immediate relative reduction of 66% (p < .0001) in pain-related residual PIPs. A significant decreasing time trend was observed during the post-implementation period. Post-implementation, 1683 recommendations were given over 1 year with an acceptance rate of 74.3%., Conclusions: We proved that the CMA approach reduced the number of pain-related residual PIPs. More pharmacist involvement and the use of clinical rules during hospital stay should be further promoted to optimize appropriate prescribing of analgesics., Significance: Prescribing of analgesics should be improved in inpatients to optimize pain control and to reduce iatrogenic harm. The Check of Medication Appropriateness (CMA) approach, comprising a clinical rule-based screening for patients at risk and a targeted medication review by pharmacists, reduced the number of pain-related potentially inappropriate prescriptions in a highly significant and sustained manner. This study presents the opportunities of a centralized clinical pharmacy service to help clinicians to further improve analgesic prescribing., (© 2020 European Pain Federation - EFIC®.)

Aim: To explore fracture outcomes with tapentadol or oxycodone, two opioids with differing mechanisms of action. Materials & methods: Retrospective cohort pilot study, using MarketScan ® Commercial and Medicare Supplemental claims databases, on patients with postoperative pain, back pain, or osteoarthritis and ≥1 claim for tapentadol (n = 16,457), oxycodone (n = 1,356,920), or both (n = 15,893) between June 2009 and December 2015. Results: During 266,826 and 9,007,889 days of tapentadol and oxycodone treatment, patients evidenced 1080 and 72,275 fractures, respectively. Fracture rates per treatment-year were 1.512 for tapentadol and 3.013 for oxycodone. Conclusion: Examination of administrative claims has inherent limitations, but this exploratory analysis indicates a lower fracture rate with tapentadol than oxycodone in the analyzed dataset, which needs confirmation by further clinical trials.

Central poststroke pain (CPSP) is a debilitating and often treatment-refractory condition that affects numerous stroke patients. The location of lesions most likely to cause pain and the identity of the functional brain networks that they impinge upon remain incompletely understood. We aimed to (1) elucidate which lesion locations are most frequently accompanied by pain; (2) explore CPSP-associated functional networks; and (3) examine how neuromodulation interacts with these networks. This multisite study investigated 17 CPSP patients who received deep brain stimulation (DBS; n = 12) or motor cortex stimulation (MCS; n = 5). Pain-causing lesions were manually segmented and normalized to standard space. To identify areas linked to high risk of pain, the locations of CPSP lesions and 220 control lesions were compared using voxelwise odds ratio mapping. The functional connectivity of pain-causing lesions was obtained using a large (n = 1000) normative resting-state functional MRI connectome and compared to that of control lesions and therapeutic DBS activation volumes. Brain regions most associated with CPSP risk (highest value = 63 times) were located along the ascending somatosensory pathways. These areas and the majority of individual CPSP lesions were functionally connected to anterior/middle cingulate cortex, insula, thalamus, and inferior parietal lobule (PBonferroni < 0.05). The extent of connectivity to the thalamus, inferior parietal lobule, and precuneus also differed between CPSP and control lesions (PBonferroni < 0.05). Posterior insula and thalamus shared connectivity with both CPSP lesions and pain-alleviating DBS activation volumes (PBonferroni < 0.05). These findings further clarify the topography and functional connectivity of pain-causing brain lesions, and provide new insights into the network-level mechanism of CPSP neuromodulation.

Objectives: Management of pain is suboptimal in many prehospital and emergency department settings, and European guidelines are lacking. We carried out the Consensus On Management of PAin Caused by Trauma (COMPACT) Delphi initiative to gain insights into the factors physicians consider important when selecting analgesics for trauma pain., Patients and Methods: A pan-European panel of experts in emergency medicine or pain (N = 31) was recruited to participate in the COMPACT Delphi initiative. In round 1, panelists supplied free-text responses to an open question about the attributes of analgesics for emergency pain relief favored by physicians. Common themes were consolidated into factors. In round 2, factors rated important by more than 75% of the panel were taken forward into round 3. In round 3, the point at which the consensus was achieved was defined a priori as at least 75% of panelists agreeing or strongly agreeing that a factor was important., Results: Twenty-nine experts participated, representing 12 European countries and with a mean (SD) of 20 (8.6) years of clinical experience. Most worked in an emergency department (79.3%). The consensus was achieved for 10 factors that were important to consider when selecting analgesics for trauma pain relief. The highest level of consensus was achieved for 'efficacy' (100%), followed by 'safety and tolerability' (96.6%), and 'ease of use' (93.1%)., Conclusion: These findings may facilitate the development of evidence-based guidelines supporting the provision of pain management in prehospital, emergency department, and critical care settings.

Competing Interests: Competing interests: None declared.

Background and Objective: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease., Methods: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation., Results and Conclusions: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering., Significance: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe., (© 2018 European Pain Federation - EFIC®.)

Background: Opioid-induced bowel dysfunction is a complication of opioid therapy, in which constipation is the most common and problematic symptom. However, it is frequently under-recognised and thus effective management is often not instituted despite a number of treatment options., Objective: The central objective of this study is to provide a summary of the pathophysiology and clinical evaluation of opioid-induced constipation and to provide a pragmatic management algorithm for day-to-day clinical practice., Methods: This summary and the treatment algorithm is based on the opinion of a European expert panel evaluating current evidence in the literature., Results: The pathophysiology of opioid-induced constipation is multi-faceted. The key aspect of managing opioid-induced constipation is early recognition. Specific management includes increasing fluid intake, exercise and standard laxatives as well as addressing exacerbating factors. The Bowel Function Index is a useful way of objectively evaluating severity of opioid-induced constipation and monitoring response. Second-line treatments can be considered in those with recalcitrant symptoms, which include gut-restricted or peripherally acting mu-opioid receptor antagonists. However, a combination of interventions may be needed., Conclusion: Opioid-induced constipation is a common, yet under-recognised and undertreated, complication of opioid therapy. We provide a pragmatic step-wise approach to opioid-induced constipation, which should simplify management for clinicians.

Introduction: Over the past decades, awareness on the importance of educational interventions in cancer pain management has increased. However, education is often restricted to biomedical pain management instructions. A more modern educational approach, also known as pain neuroscience education (PNE), explains pain from a biopsychosocial perspective. We hypothesise that this more comprehensive educational approach in the early treatment phase of breast cancer will lead to more beneficial effects for cancer pain management. Therefore, the aim of the present study is to investigate the effectiveness of this PNE intervention, in addition to best evidence physical therapy modalities for treatment and prevention of pain, physical, emotional and work-related functioning after breast cancer surgery, compared with a traditional biomedical educational intervention., Methods: A double-blinded randomised controlled trial has been started in November 2017 at the University Hospitals of Leuven. Immediately after breast cancer surgery, all participants (n=184) receive a 12-week intensive standard physical therapy programme. They receive three additional refresher sessions at 6, 8 and 12 months postsurgery. In addition, participants receive three educational sessions during the first-month postsurgery and three 'booster sessions' at 6, 8 and 12 months postsurgery. In the intervention group, the content of the education sessions is based on the modern PNE approach. Whereas in the control group, the education is based on the traditional biomedical approach. The primary outcome parameter is pain-related disability 1 year after surgery. Secondary outcomes related to other dimensions of pain, physical, emotional and work-related functioning at 1-week, 4, 6, 8, 12 and 18 months postsurgery., Ethics and Dissemination: The study will be conducted in accordance with the Declaration of Helsinki. This protocol has been approved by the ethical committee of the University Hospitals of Leuven. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses., Trial Registration Number: NCT03351075., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cannabis-based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis-based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis-based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis-based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline-recommended first- and second-line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non-neuropathic noncancer pain), the use of cannabis-based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis-based medicines should be terminated., Significance: This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis-based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients., (© 2018 European Pain Federation - EFIC®.)

Objective: Acute postoperative pain is experienced by the majority of hospitalized patients undergoing surgical procedures, with many reporting inadequate pain relief and/or high levels of dissatisfaction with their pain management. Patient-controlled analgesia (PCA) ensures patient involvement in acute pain control, a key component for implementing a quality management system. This narrative article overviews the clinical evidence for conventional PCA and briefly discusses new, non-invasive PCA systems, namely the sufentanil sublingual tablet system (SSTS) and the fentanyl iontophoretic transdermal system (FITS)., Methods: A Medline literature search ("patient-controlled analgesia" and "acute postoperative pain") was conducted to 1 April 2017; results from the main clinical trials are discussed. Additional literature was identified from the reference lists of cited publications., Results: Moderate to low quality evidence supports opioid-based intravenous PCA as an efficacious alternative to non-patient-controlled systemic analgesia for postoperative pain. However, despite the benefits of PCA, conventional intravenous PCA is limited by system-, drug- and human-related issues. The non-invasive SSTS and FITS have demonstrated good efficacy and safety in placebo- and intravenous morphine PCA-controlled trials, and are associated with high patient/healthcare practitioner satisfaction/ease of care ratings and offer early patient mobilization., Conclusions: Evidence-based guidelines for acute postoperative pain management support the use of multimodal regimens in many situations. As effective and safe alternatives to conventional PCA, and with the added benefits of being non-invasive, easy to use and allowing early patient mobilization, the newer PCA systems may complement multimodal approaches, or potentially replace certain regimens, in hospitalized patients with acute postoperative pain.

Objective: Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of "pain chronification"., Methods: This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification., Results: Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: "Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification.", Conclusions: Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.

Background: Opioids provide effective relief from moderate-to-severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed-dose oxycodone/naloxone prolonged-release tablets (OXN PR) were designed to address the opioid class effect of opioid-induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse-deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone., Methods: A literature search was conducted to assess the evidence base for OXN PR to treat moderate-to-severe pain and its impact on bowel function, based on published clinical trials and observational studies., Results: Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate-to-severe cancer-related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease-related pain. No unanticipated safety concerns have been reported in elderly patients., Conclusions: Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate-to-severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day)., (© 2017 The Authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.)

Abdominal pain is an important symptom in most patients with pancreatic ductal adenocarcinoma (PDAC). Adequate control of pain is often unsatisfactory due to limited treatment options and significant variation in local practice, emphasizing the need for a multidisciplinary approach. This review contends that improvement in the management of PDAC pain will result from a synthesis of best practice and evidence around the world in a multidisciplinary way. To improve clinical utility and evaluation, the evidence was rated according to the GRADE guidelines by a group of international experts. An algorithm is presented, which brings together all currently available treatment options. Pain is best treated early on with analgesics with most patients requiring opioids, but neurolytic procedures are often required later in the disease course. Celiac plexus neurolysis offers medium term relief in a substantial number of patients, but other procedures such as splanchnicectomy are also available. Palliative chemotherapy also provides pain relief as a collateral benefit. It is stressed that the assessment of pain must take into account the broader context of other physical and psychological symptoms. Adjunctive treatments for pain, depression and anxiety as well as radiotherapy, endoscopic therapy and neuromodulation may be required in selected patients. There are few comparative studies to help define which combination and order of these treatment options should be applied. New pain therapies are emerging and could for example target neural transmitters. However, until better methods are available, management of pain should be individualized in a multidisciplinary setting to ensure optimal care., (Copyright © 2018 IAP and EPC. All rights reserved.)

The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in patients with opioid-induced constipation and chronic noncancer pain in a 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on a routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo (n = 623). The primary endpoint was summary measures of treatment-emergent adverse events (AEs). Additional endpoints included opioid withdrawal on the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale, pain intensity on Numeric Rating Scale, frequency of bowel movements, and constipation-related symptoms and quality of life on the Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life scales, respectively. Treatment-emergent AEs (naldemedine, 68.4% vs placebo, 72.1%; difference: -3.6% [95% confidence interval: -8.7 to 1.5]) and treatment-emergent AEs leading to study discontinuation (6.3% vs 5.8%; difference: 0.5% [-2.2 to 3.1)] were reported for similar proportions of patients. Diarrhea was reported more frequently with naldemedine (11.0%) vs placebo (5.3%; difference: 5.6% [2.6-8.6]). There were no meaningful differences between groups in opioid withdrawal or pain intensity. Sustained significant improvements in bowel movement frequency and overall constipation-related symptoms and quality of life were observed with naldemedine (P ≤ 0.0001 vs placebo at all time points). Naldemedine was generally well tolerated for 52 weeks and did not interfere with opioid-mediated analgesia or precipitate opioid withdrawal. Naldemedine significantly increased bowel movement frequency, improved symptomatic burden of opioid-induced constipation, and increased patients' quality of life vs placebo.

Objective: Hypothalamic-pituitary-adrenal axis dysfunction may play a role in fibromyalgia (FM) pathogenesis but it remains understudied in this disorder. Furthermore, early childhood adversities (ECA) are common in FM, but whether they moderate stress reactivity is unknown. Hence, we investigated cortisol and subjective responses to acute psychosocial stress in FM and controls, while adjusting for ECA., Methods: Twenty-seven female FM patients and 24 age-matched female controls were recruited in a tertiary care center and through advertisements, respectively. The Childhood Trauma Questionnaire was used to measure ECA history. Salivary cortisol levels and subjective stress ratings were measured at multiple time points before and after the Trier Social Stress Test (TSST) was administered., Results: Significant main effects of group [F(1,43) = 7.04, p = .011, lower in FM] and ECA [F(1,43) = 5.18, p = .028, higher in participants with ECA] were found for cortisol responses. When excluding controls with ECA (n = 5), a significant group-by-time interaction was found [F(6,39) = 2.60, p = .032], driven by a blunted response to the stressor in FM compared with controls (p = .037). For subjective stress responses, a significant main effect of group [F(1,45) = 10.69, p = .002, higher in FM] and a trend toward a group-by-time interaction effect [F(6,45) = 2.05, p = .078, higher in FM 30 minutes before and 30 and 75 minutes after the TSST, and impaired recovery (difference immediately after - 30 minutes after the TSST) in FM] were found., Conclusions: Blunted cortisol responsivity to the TSST was observed in FM patients compared with controls without ECA. FM patients had higher subjective stress levels compared with controls, particularly at baseline and during recovery from the TSST. In FM patients, ECA history was not associated with cortisol or subjective stress levels or with responsivity to the TSST. Future research should investigate the mechanisms underlying hypothalamic-pituitary-adrenal axis dysregulation in FM.

Despite the introduction of evidence-based recommendations for postoperative pain management (POPM), the consensus is that pain control remains suboptimal. Barriers to achieving patient-satisfactory analgesia include deficient knowledge regarding POPM among staff, lack of instructions, insufficient pain assessments and sub-optimal treatment. Effective monitoring of POPM is essential to enable policy makers and healthcare providers to improve the quality of care. Quality indicators (QIs) are quantitative measures of clinical practice that can monitor, evaluate and guide the quality of care provided to patients. QIs can be used to assess various aspects relating to the care process and they have proven useful in improving health outcomes in diseases such as myocardial infarction. In this commentary we critically analyze the evidence regarding the use of QIs in acute POPM based upon the experience of pain specialists from Europe and the USA who are members of the Change Pain Advisory Board. We also undertook a literature review to see what has been published on QIs in acute pain with the goal of assessing which QIs have been developed and used, and which ones have been successful/unsuccessful. In the hospital sector the development and implementation of QIs is complex. The nature of POPM requires a highly trained, multidisciplinary team and it is at this level that major improvements can be made. Greater involvement of patients regarding pain management is also seen as a priority area for improving clinical outcomes. Changes in structure and processes to deliver high-level quality care need to be regularly audited to ensure translation into better outcomes. QIs can help drive this process by providing an indicator of current levels of performance. In addition, outcomes QIs can be used to benchmark levels of performance between different healthcare providers.

Objective: To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction., Setting: Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction.", Methods: A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system., Results: From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioid-induced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide guidance on clinical best practice in the management of patients with opioid-induced constipation and opioid-induced bowel dysfunction., Conclusions: In recent years, more insight has been gained in the pathophysiology of this "entity"; new treatment approaches have been developed, but guidelines on clinical best practice are still lacking. Current knowledge is insufficient regarding management of the opioid side effects on the upper gastrointestinal tract, but recommendations can be derived from what we know at present., (© 2016 American Academy of Pain Medicine.)