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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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). [ABSTRACT FROM AUTHOR]

Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed.Diagnosis: Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects.Conclusions: This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and anticonvulsants), supplemented by appropriate non-pharmacological measures such as exercise programs, manual therapies, behavioral therapies, interventional pain management and traction. Surgery may be appropriate in carefully selected patients. [ABSTRACT FROM AUTHOR]

Central poststroke pain (CPSP) is a severe type of neuropathic pain that can develop after stroke and is difficult to treat. Research into its underlying mechanisms and treatment options could benefit from a valid CPSP animal model. Nine different CPSP animal models have been published, but there are relatively few reports on successful reproductions of these models and so far only little advances in the understanding or the management of CPSP have been made relying on these models. In general, the construct validity (similarity in underlying mechanisms) of these CPSP animal models is relatively high, although this cannot be evaluated into depth because of lack of understanding the mechanisms through which thalamic stroke can lead to CPSP. The face validity (symptom similarity) is relatively low, mainly because pain in these models is tested almost exclusively through evoked mechanical/thermal hypersensitivity assessed by reflexive measures and given the conflicting results with similar tests in patients with CPSP. The predictive validity (similarity in treatment efficacy) has not been evaluated in most models and incorporates difficulties that are specific to CPSP. We compare the different models regarding these types of validity and discuss the robustness, reproducibility, and problems regarding the design and reporting of the articles establishing these models. We conclude with various proposals on how to improve the validity and reproducibility of CPSP animal models. Until further improvements are achieved, prudence is called for in interpreting results obtained through these models. [ABSTRACT FROM AUTHOR]

In patients managed with opioids for chronic pain, opioid-induced bowel dysfunction-specifically, opioid-induced constipation (OIC)-is a common side effect, which has a significant impact on quality of life (QoL). The most recent developments for management of OIC are opioid antagonists, including naloxone, a competitive antagonist of peripheral opioid receptors that reverses opioid-induced peripheral gastrointestinal (GI) effects. A prolonged-release formulation of naloxone is available in combination with oxycodone (OXN PR). To review the specific role of OXN PR in the management of chronic pain and OIC and its impact on QoL and healthcare costs, a review of available relevant literature was conducted. Healthcare costs can be up to ten times higher for patients with GI events than for those without. Assessment of QoL in patients with OIC is essential, and multiple tools for its evaluation are available. The Bowel Function Index (BFI), a tool that was specifically developed and validated to measure bowel function in patients with OIC, can be an indication of QoL. In patients with moderate-to-severe chronic pain, randomized trials have demonstrated that OXN PR has equal analgesic efficacy and safety, but results in improved bowel function, compared with prolonged-release oxycodone (Oxy PR) alone. In conclusion, randomized studies using the BFI, as well as real-world clinical practice observations, have demonstrated improved QoL for patients taking OXN PR. This combination should allow more patients to benefit from the analgesic efficacy of opioid therapy and should minimize the side effects of constipation that correspond to improvements in QoL and healthcare offsets. [ABSTRACT FROM AUTHOR]

Chronic low back pain (CLBP) is a highly prevalent, costly and disabling condition that is associated with high levels of health-care resource utilization. Over the past few decades, there has been a paradigm shift in our understanding of CLBP. Nowadays, this condition is accepted as a biopsychosocial phenomenon in which anatomical injury interplays with psychosocial factors. The considerable progress made in elucidating the aetiology of low back pain and the sharp increase in related health-care costs have not translated into a decreased prevalence of CLBP or the development of therapies with markedly improved efficacy and safety. Classic medical-technical interventions for CLBP always need to be placed in a broader therapeutic framework comprising physical, psychosocial and behavioural strategies, and must address the patient's welfare in a holistic context. A common key finding in the literature on these interventions for CLBP is their disappointing magnitude of pain reduction and gain in functionality. This Review summarizes general concepts of CLBP and focuses on evidence supporting the classic medical-technical approaches to CLBP; that is, pharmacotherapy, interventional pain management and surgery. [ABSTRACT FROM AUTHOR]

Chronic low back pain (CLBP) is a highly prevalent, costly and disabling condition that is associated with high levels of health-care resource utilization. Over the past few decades, there has been a paradigm shift in our understanding of CLBP. Nowadays, this condition is accepted as a biopsychosocial phenomenon in which anatomical injury interplays with psychosocial factors. The considerable progress made in elucidating the aetiology of low back pain and the sharp increase in related health-care costs have not translated into a decreased prevalence of CLBP or the development of therapies with markedly improved efficacy and safety. Classic medical–technical interventions for CLBP always need to be placed in a broader therapeutic framework comprising physical, psychosocial and behavioural strategies, and must address the patient's welfare in a holistic context. A common key finding in the literature on these interventions for CLBP is their disappointing magnitude of pain reduction and gain in functionality. This Review summarizes general concepts of CLBP and focuses on evidence supporting the classic medical–technical approaches to CLBP; that is, pharmacotherapy, interventional pain management and surgery. [ABSTRACT FROM AUTHOR]

The article reports on the case of a chronic intrathecal opioid therapy patient who had an unusual symptomatic catheter tip mass. Topics include symptomatic intrathecal granulomas associated within trathecal pumps, the association between granulomas and intrathecal opioid treatment, and the role of magnetic resonance imaging as the standard for diagnosing intrathecal granulomas.

Chronic pain is a debilitating condition with a multidimensional impact on the lives of patients, their families and communities. The public health burden of chronic pain is gathering recognition as a major healthcare problem in its own right and deserves closer attention. The challenge in treating chronic pain is to provide effective clinical management of a complex, multifaceted set of conditions that require a coordinated strategy of care. Epidemiological data and patient surveys have highlighted the areas of pain management that might be improved. These include a need for better understanding and documentation of the symptoms of chronic pain, standardized levels of care, improved communication among clinical personnel and with patients, and an updated education program for clinicians. For these reasons, new strategies aimed at improving the standards of pain management are needed. The Pain Associates' International Network (P.A.I.N.) Initiative was set up to devise practical methods for improving the quality of pain management for patients. These strategies have recently been put into practice through a number of activities: P.A.I.N. Workshops are meetings of international pain management professionals dedicated to discussing current management strategies and producing consensus recommendations for improving standards of care; P.A.I.N. Quality is a unique software program designed to help treating clinicians to document patient data and derive effective treatment plans; P.A.I.N. Online provides a web site forum for discussion of pain management topics; and P.A.I.N. Management is a clinician education program providing up-to-date training in pain management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the essences of rehabilitation is enhancing a persons' functioning and participation in society, including work. According to the International Classification of Functioning, Disability and Health (ICF), participation can be influenced by a wide range of factors, including pain. In many patients with a pain complaint a neuropathic pain component is present. To steer (vocational) rehabilitation, it is important to recognize the presence of neuropathic pain. Expensive and time-consuming instrumental tests (e.g. Quantitative Sensory Testing) to identify presence of neuropathic pain are available in specialized centers but not applicable in daily clinical practice in rehabilitation settings. The aim of this manuscript is to give an overview of alternative screening and assessment methods of neuropathic pain that are applicable in a daily clinical setting and for the different professionals who may be involved in rehabilitation (e.g., physical therapists, occupation! therapists, counselors, etc). The first part elaborates on the definition of neuropathic pain and common terminology. Second, basic anatomy and physiology related to neuropathic pain are presented needed to understand neuropathic pain. Third, the relevant aspects of clinical history and clinical examination are discussed. Finally, screening tools for neuropathic pain and alternative clinical assessments methods for Quantitative Sensory Testing are presented. [ABSTRACT FROM AUTHOR]

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. To assess psychometric properties of the PDI-DLV after breast cancer surgery. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Adding 6 sessions of pain neuroscience education to standard physiotherapy after breast cancer surgery did not result in a better course of functioning compared with biomedical pain education. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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). Significant but weak (rs < 0.30) correlations were found between total DN4 score and QST results at the inner upper arm for detection of sharp stimuli (rs = 0.227), cold stimuli (rs = −0.186), and painful heat stimuli (rs = 0.179), as well as between QST evaluating conditioned pain modulation and the Margolis Pain Diagram on one hand (rs = 0.176) and minimum-maximum pain intensity differences (VAS) on the other (rs = −0.170). 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. Clinicians 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Current approaches to the management of pain due to amputation are presented by two Spanish pain specialists with additional commentaries on care of such patients by pain specialists from Belgium and the United Kingdom. Contemporary pharmacotherapy and nondrug interventions are described. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 opioidinduced 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. [ABSTRACT FROM AUTHOR]

Aim To develop a non-invasive, safe and reproducible target-engagement biomarker for future TRPA1 antagonists in healthy volunteers. Methods Dose finding ( n = 11): 3%, 10%, and 30% cinnamaldehyde (CA) and placebo (= vehicle) was topically applied on the right forearm. One-way ANOVA with post-hoc Bonferroni was used to compare between doses. Reproducibility: 10% CA doses were topically applied during one visit on both arms ( n = 10) or during two visits ( n = 23) separated by a washout period of 7 days. CA-induced dermal blood flow (DBF) was assessed by laser Doppler imaging (LDI) at baseline and at 10, 20, 30, 40 and 50 min post-CA. Paired t-test was used to compare between arms or visits. Concordance correlation coefficient (CCC) was calculated to assess reproducibility. Data are expressed as percent change from baseline (mean ± 95% CI). Results All three doses increased DBF compared to vehicle at all time-points, with the maximum response at 10-20 min post-CA. Dose response was found when comparing AUC0-50min of 30% CA (51 364 ± 8475%*min) with 10% CA (32 239 ± 8034%*min, P = 0.03) and 3% CA (30 226 ± 11 958%*min, P = 0.015). 10% CA was chosen as an effective and safe dose. DBF response to 10% CA was found to be reproducible between arms (AUC0-50min, CCC = 0.91) and visits (AUC0-50min, CCC = 0.83). Based on sample size calculations, this model allows a change in CA-induced DBF of 30-50% to be detected between two independent groups of maximum 10-15 subjects with 80% power. Conclusions Evaluation of CA-induced changes in DBF offers a safe, non-invasive and reproducible target-engagement biomarker in vivo in humans to evaluate TRPA1 antagonists. [ABSTRACT FROM AUTHOR]

Opioids are increasingly used for treatment of chronic pain. However, they are only effective in a subset of patients and have multiple side effects. Thus, studies using biomarkers for response are highly warranted. The current study prospectively examined 63 opioid-naïve patients initiating opioid use for diverse types of chronic pain at five European centers. Quantitative sensory testing, electroencephalography (EEG) recordings, and assessment of pain catastrophizing were performed prior to treatment. The co-primary outcomes were change from baseline in ratings of chronic pain and quality of life after 14 days of opioid treatment. Secondary outcomes included patient’s global impression of clinical change and side effects. Logistic regression models adjusted for age and sex were used to identify biomarkers predictive for successful treatment, defined as at least a 30% reduction in average pain intensity or an improvement in quality of life of at least 10 scale points. Fifty-nine patients (94%) completed the study. The mean age was 55 ± 16 years and 69% were females. Pain reduction was predicted by cold pain intensity (OR: 0.69; P = 0.01), pain catastrophizing (OR: 0.82; P = 0.03), relative delta (OR: 0.76; P = 0.03) and beta EEG activity (OR: 1.18; P = 0.04) induced by experimental cold pain. None of the study variables were related to improvement in quality of life. For the first time, individual pain processing characteristics have been linked to opioid response in a mixed chronic pain population. This has the potential to personalize treatment of chronic pain and restrict opioid use to patients with high likelihood for response. [ABSTRACT FROM AUTHOR]

Poor management of post-operative acute pain can contribute to medical complications including pneumonia, deep vein thrombosis, infection and delayed healing, as well as the development of chronic pain. It is therefore important that all patients undergoing surgery should receive adequate pain management. However, evidence suggests this is not currently the case; between 10% and 50% of patients develop chronic pain after various common operations, and one recent US study recorded >80% of patients experiencing post-operative pain. At the first meeting of the acute chapter of the Change Pain Advisory Board, key priorities for improving post-operative pain management were identified in four different areas. Firstly, patients should be more involved in decisions regarding their own treatment, particularly when fateful alternatives are being considered. For this to be meaningful, relevant information should be provided so they are well informed about the various options available. Good physician/patient communication is also essential. Secondly, better professional education and training of the various members of the multidisciplinary pain management team would enhance their skills and knowledge, and thereby improve patient care. Thirdly, there is scope for optimizing treatment. Examples include the use of synergistic analgesia to target pain at different points along pain pathways, more widespread adoption of patient-controlled analgesia, and the use of minimally invasive rather than open surgery. Fourthly, organizational change could provide similar benefits; introducing acute pain services and increasing their availability towards the 24 hours/day ideal, greater adherence to protocols, increased use of patient-reported outcomes, and greater receptivity to technological advances would all help to enhance performance and increase patient satisfaction. It must be acknowledged that implementing these recommendations would incur a considerable cost that purchasers of healthcare may be unwilling or unable to finance. Nevertheless, change is under way and the political will exists for it to continue. [ABSTRACT FROM PUBLISHER]

Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses’, pharmacists’ and physiotherapists’ skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late. Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels – for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain. Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain – it is vital they continue. [ABSTRACT FROM PUBLISHER]

Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients' reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient's rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms - rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level. [ABSTRACT FROM AUTHOR]

In many countries, the number of elderly people has increased rapidly in recent years and this is expected to continue; it has been predicted that almost a quarter of the population in the European Union will be over 65 years of age in 2035. Many elderly people suffer from chronic pain but it is regularly under-treated, partly because managing these patients is often complex. This paper outlines the extent of untreated pain in this population and the consequent reduction in quality of life, before articulating the reasons why it is poorly or inaccurately diagnosed. These include the patient's unwillingness to complain, atypical pain presentations, multiple morbidities and cognitive decline. Successful pain management depends upon accurate diagnosis, which is based upon a complete history and thorough physical examination, as well as an assessment of psychosocial functioning. Poor physician/patient communication can be improved by using standardized instruments to establish individual treatment targets and measure progress towards them. User-friendly observational instruments may be valuable for patients with dementia. In line with the widely accepted biopsychosocial model of pain, a multidisciplinary approach to pain management is recommended, with pharmacotherapy, psychological support, physical rehabilitation and interventional procedures available if required. Declining organ function and other physiological changes require lower initial doses of analgesics and less frequent dosing intervals, and the physician must be aware of all medications that the patient is taking, in order to avoid drug/drug interactions. Non-adherence to treatment is common, and various strategies can be employed to improve it; involving the elderly patient's caregivers and family, using medication systems such as pill-boxes, or even sending text messages. In the long term, the teaching of pain medicine needs to be improved - particularly in the use of opioids - both at undergraduate level and after qualification. [ABSTRACT FROM AUTHOR]

Background Self-critical perfectionistic personality features have been shown to influence the onset and perpetuation of pain symptoms. However, no study to date has investigated whether these personality features are associated with treatment response in chronic pain. Methods Using a naturalistic pre-post design, the present study examined the effect of self-critical perfectionism on treatment outcome in terms of self-reported pain. The study was conducted in a sample of 53 chronic non-cancer pain patients who followed Multidisciplinary Pain Education Program ( MPEP), a brief, 2-week cognitive-behaviorally based psycho-educational intervention for chronic pain that was recently found to be effective in reducing pain severity. Pre- and post-treatment pain intensity levels were assessed with the visual analog scale of the McGill Pain Questionnaire-Short Form. Results Pretreatment self-critical perfectionism was significantly associated with negative treatment outcome, even after taking into account pretreatment levels of depression. Conclusion Results suggest that self-critical perfectionistic personality features may negatively interfere with treatment response in patients with chronic pain. Thus, findings indicate that chronic pain patients with high levels of self-critical perfectionism may benefit less from brief interventions such as MPEP, and therefore may need more intensive and tailored treatment. [ABSTRACT FROM AUTHOR]

Chronic pain is currently under-diagnosed and under-treated, partly because doctors' training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain. [ABSTRACT FROM AUTHOR]

AbstractBackground:Despite limited empirical support, chronic pain has traditionally been defined mainly on the basis of its duration, which takes no account of the causative mechanisms or its clinical significance.Scope:For this commentary on current pain management practice, the CHANGE PAIN Advisory Board considered the evidence for adopting a prognostic definition of chronic pain. The rationale underlying this approach is to take psychological and behavioural factors into account, as well as the multidimensional nature of pain. Measures of pain intensity, interference with everyday activities, role disability, depression, duration and number of pain sites are used to calculate a risk score, which indicates the likelihood of a patient having pain in the future. The consistency of a prognostic definition with the concept of integrated patient care was also considered.Findings:When this method was compared with the number of pain days experienced over the previous 6 months – in patients with back pain, headache or orofacial pain – it was a better predictor of clinically significant pain 6 months later for all three pain conditions. Further evidence supporting this approach is that several factors other than the duration of pain have been shown to be important prognostic indicators, including unemployment, functional disability, anxiety and self-rated health. The use of a multifactorial risk score may also suggest specific measures to improve outcomes, such as addressing emotional distress. These measures should be undertaken as part of an integrated pain management strategy; chronic pain is a biopsychosocial phenomenon and all aspects of the patient’s pain must be dealt with appropriately and simultaneously for treatment to be effective.Conclusion:The implementation of a prognostic definition and wider adoption of integrated care could bring significant advantages. However, these measures require improved training in pain management and structural revision of specialist facilities, for which political support is essential. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain. Methods: This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in pain (0-10 NRS) as the predictor and scores on the following PRO measures as the outcome: Pain Interference Index; Hospital Anxiety and Depression Scale anxiety and depression subscales; Medical Outcomes Study-Sleep Scale 9-item Sleep Problems Index and Sleep Disturbance subscale; and Daily Sleep Interference Scale (0-10 NRS). Results: Change in pain severity showed clear, direct relationships with changes in function, anxiety, depression, and sleep PROs, all of which were statistically significant (P <.001). Results from subgroup analyses (≥30% or ≥50% pain responders, pregabalin or placebo treatment, age ≤ 51 years or > 51 years) tended to be consistent with results from the overall sample. Conclusions: Overall, a direct relationship exists between pain and various aspects of patient's well-being and functioning, which can provide a quantitative assessment of how improvements in pain may be expected to relate to other patient outcomes. (http://ClinicalTrials.gov Identifier number NCT00292188; EudraCT #2005-003048-78). [ABSTRACT FROM AUTHOR]

Abstract: Background: In chronic non-malignant pain, medication is often used as an important cornerstone of the treatment. Medication non-adherence is a frequent problem in chronic conditions. In patients with chronic non-malignant pain, medication non-adherence ranges between 8% and 53%. Two types of non-adherence can be identified: underuse and overuse of pain medication. Objective: To examine determinants of both medication underuse and overuse non-adherence in patients with chronic non-malignant pain, with a focus on factors related to all five categories of determinants of medication non-adherence simultaneously, as proposed by the WHO. Design: A multicenter cross-sectional study. Settings: Three multidisciplinary outpatient pain centers in Flanders, Belgium. Participants: A total of 265 patients with chronic non-malignant pain participated in the study. Methods: Medication non-adherence was assessed by a self-report interview. Associations of socio-economic, treatment related, condition related, patient related and health care system related factors with medication underuse or overuse were determined by building two separate multivariable binary logistic regression models. Results: Thirty eight percent of the patients were fully adherent. Based on multivariable analyses, underuse was significantly associated with more prescribed analgesics (OR=2.303), self-medication (OR=4.679), lower pain intensity (OR=0.821), active coping strategies (OR=1.132) and lack of information (OR=0.268). Overuse of medication was associated with more prescribed analgesics (OR=1.645) and current smoking (OR=2.744). Conclusion: Patients underusing or overusing their medication do have a different risk profile. The set of determinants of non-adherence, proposed by WHO, is suitable to study determinants of underuse, but the framework is less suitable to study determinants of medication overuse. [Copyright &y& Elsevier]

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. [ABSTRACT FROM AUTHOR]

Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week (with >or=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to >or=30 mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia. [ABSTRACT FROM AUTHOR]

Abstract: Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week (with ⩾25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to ⩾30mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P <0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia. [Copyright &y& Elsevier]

Abstract: Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores −1.48 points vs. −0.52 points on a 0–10 Numerical Rating Scale (p =0.004; 95% CI: −1.59, −0.32). Improvements in Neuropathic Pain Scale composite score (p =0.007), sleep NRS (p =0.001), dynamic allodynia (p =0.042), punctate allodynia (p =0.021), Pain Disability Index (p =0.003) and Patient’s Global Impression of Change (p <0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks. [Copyright &y& Elsevier]

Meningioma mostly present with localised pain associated with signs of spinal cord compression. We present a case of a 72 year old woman with a thoracal meningioma with an atypical manifestation: radicular thoracal pain with signs of mechanical hyperalgesia and allodynia without any signs of spinal cord compression. Diagnosis was made by MRI-scan of the dorsal spine. After neurosurgical resection there was a complete recovery. We like to stress the importance of providing detailed information on clinical cases, especially with an atypical manifestation. We review the literature published on meningioma and discuss the most important symptoms and signs. [ABSTRACT FROM AUTHOR]