Neuropathic pain (NP) is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity of NP conditions is often worse at night. Some evidence suggests that the pineal hormone, melatonin, may reduce pain in clinical settings. We conducted a clinical trial to evaluate the efficacy of melatonin for NP. Using a double-blind, placebo-controlled, crossover design, 31 adults with NP were randomly allocated to 1 of 2 sequences of treatment with melatonin and placebo. During each of 2 treatment periods, participants took capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome was mean daily pain intensity (0-10) at maximally tolerated doses (MTD) during each period. Secondary outcomes, assessed at MTD, included adverse events, and measures of sleep, mood, and quality of life. Thirty-one participants were recruited, and 30 participants completed both treatment periods of the trial. The mean maximal tolerated dose of melatonin in this trial was 11.9 mg/day. Treatment-emergent adverse events with melatonin were infrequent and not statistically different from placebo. At MTD, mean daily pain (standard error) was 4.1 (0.3) for melatonin and 4.2 (0.3) for placebo ( P = 0.8). There were no statistically significant differences between placebo and melatonin for any secondary outcomes. Overall, the results of this trial do not provide any evidence to suggest promise for melatonin as an effective treatment for NP.

OBJECTIVES:Activity management is an important treatment component in chronic pain programs. However, there are shortcomings in measures of this construct, leading to inconsistencies in research findings. Here, we describe the development of the Activity Management Inventory for Pain (AMI-P). MATERIALS AND METHODS:The AMI-P was developed by a group of international researchers with extensive expertise in both chronic pain and activity management. The initial evaluation of the AMI-P items included 2 studies that were both conducted in Canadian tertiary pain care centers. RESULTS:The resulting 20-item measure has 3 behavior scales (Rest, Alternating Activity, and Planned Activity), and 4 goal scales (Feel Less Pain, Get More Done, Complete the Task, and Save Energy). The behavior scales evidenced marginal to good internal consistency and test-retest reliability, and a moderate positive association with an existing pacing measure. The Rest and Alternating Activity scales were associated with greater pain interference, the Alternating Activity and Planned Activity scales were associated with less satisfaction with social roles, and the Planned Activity scale was associated with fewer depressive symptoms. The Alternating Activity scale increased significantly from pretreatment to posttreatment. All goal scales were positively associated with all behavior scales. The Feel Less Pain goal scale was positively associated with measures of avoidance and pain interference, while the Get More Done goal scale was negatively associated with measures of depressive symptoms and overdoing. DISCUSSION:The findings support the reliability and validity of the AMI-P scales, while also highlighting the complexity and multidimensional aspects of activity management.

Introduction Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30–60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)–pregabalin (PGB) combination in participants with fibromyalgia.Methods and analysis This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT–PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT–PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0–10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).Ethics and dissemination This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen’s University Health Sciences Research Ethics Board (Queen’s HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.Trial registration number This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

STUDY DESIGN:Clinical practice guidelines.OBJECTIVES:The objective was to update the 2016 version of the Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI).SETTING:The guidelines are relevant for inpatient, outpatient and community SCI rehabilitation settings in Canada.METHODS:The guidelines were updated in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations.RESULTS:The working group identified and reviewed 46 additional relevant articles published since the last version of the guidelines. The panel agreed on 3 new screening and diagnosis recommendations and 8 new treatment recommendations. Two key changes to these treatment recommendations included the introduction of general treatment principles and a new treatment recommendation classification system. No new recommendations to model of care were made.CONCLUSIONS:The CanPainSCI recommendations for the management of neuropathic pain after SCI should be used to inform practice.

Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.

Introduction Evidence suggests a role for Central nervous system glia in pain transmission and in augmenting maladaptive opioid effects. Identification of drugs that modulate glia has guided the evaluation of glial suppression as a pain management strategy. This planned systematic review will describe evidence of the efficacy and adverse effects of glial-modulating drugs in pain management. Methods and analysis A detailed search will be conducted on the Cochrane Central Register of Controlled Trials, Medline, and Embase from their inception until the date the final searches are run to identify relevant randomised controlled trials. The reference lists of retrieved studies, as well as online trial registries, will also be searched. English language, randomised, double-blind trials comparing various glial-modulating drugs with placebo and/or other comparators, with participant-reported pain assessment, will be included. Two reviewers will independently evaluate studies for eligibility, extract data and assess trial quality and potential bias. Risk of bias will be assessed using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions. Primary outcomes for this review will include any validated measure of pain intensity and/or pain relief. Dichotomous data will be used to calculate risk ratio and number needed to treat or harm. The quality of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation. Ethics and dissemination This systematic review does not require formal ethics approval. The findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO registration number CRD42021262074.

Background Neuropathic pain (NP), a complication of several conditions (eg, diabetic neuropathy and varicella zoster), is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity in NP conditions is often worse at night. The pineal hormone melatonin has been shown to reduce pain in both preclinical and clinical settings, in addition to multiple trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome. Objective We propose to conduct a clinical trial to evaluate the efficacy and safety of melatonin for NP. Methods Using a double-blind, placebo-controlled, crossover design, 30 adults with NP will be randomly allocated to one of two sequences of treatment with melatonin and placebo. During each of the two treatment periods, participants will take capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome will be mean daily pain intensity (scored 0-10) at maximally tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTDs, will include global improvement, adverse events, mood, and quality of life. Results This trial was registered in the International Standard Randomized Controlled Trial registry May 4, 2022 (ISRCTN #16215617), attained conditional ethics approval May 9, 2022 (Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-387-22), and recruitment is set to start August 2022. Conclusions This trial will provide rigorous evidence comparing the efficacy of melatonin to that of placebo in the treatment of NP. Trial Registration ISRCTN Registry 16215617; https://www.isrctn.com/ISRCTN16215617 International Registered Report Identifier (IRRID) PRR1-10.2196/40025

BackgroundGlobally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed.MethodsUsing a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain.ResultsThere was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5-5 mg of each cannabinoid once or twice daily and titrates by 2.5-5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day.ConclusionsIn summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.

Abstract Background Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. Methods In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. Discussion This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. Trial registration ClinicalTrials.gov Identifier: NCT04221165 . Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

Purpose: Opioid addiction is a major public health concern. Chronic opioid use (COU) patterns after radiation for head and neck cancer (HNC) remain poorly understood. The aim of this study was to estimate the prevalence of COU and to identify its risk factors in patients with HNC undergoing curative-intent radiation therapy (RT) or chemoradiotherapy (CRT). Methods and Materials: We performed a systematic review and meta-analysis using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from dates of inception until January 2020. COU was defined as persistent use of opioids ≥ 3 months after treatment completion. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I2 value. Results: Seven retrospective studies, reporting on 1841 patients, met the inclusion criteria. Median age was 59.4 (range: 56.0-62.0) years with 1343 (72.9%) men and 498 (27.1%) women. Primary tumor locations included oropharynx (n = 891, 48.4%), oral cavity (n = 533, 29.0%), larynx (n = 93, 5.1%), hypopharynx (n = 32, 1.7%), and nasopharynx (n = 29, 1.6%). Eight hundred fifty-four (46.0%) patients had stage I/II and 952 (50.3%) had stage III-IV disease. Three hundred one (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of patients with HNC who developed COU post-RT/CRT was 40.7% at 3 months (95% confidence interval [CI]: 22.6%-61.7%; I2 = 97.1%) and 15.5% at 6 months (95% CI: 7.3%-29.7%; I2 = 94.3%). Oropharyngeal malignancies had the highest rate of COU based on primary tumor location (46.6%; 95% CI: 30.8%-63.1%; P < .0001). High proportions of COU were found in patients with a history of psychiatric disorder(s) (61.7%), former/current alcohol abuse (53.9%), and opioid requirements before radiation treatment (51.6%; P = .035). Conclusions: A significant proportion of patients who undergo RT for HNC suffer from COU. High-risk factors for COU include an oropharyngeal primary, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate COU are needed.

Introduction:Pain related to cancer, and its treatment, is common, may severely impair quality of life, and imposes a burden on patients, their families and caregivers, and society. Cancer-related pain is often challenging to manage, with limitations of analgesic drugs including incomplete efficacy and dose-related adverse effects.Objectives:Given problems with, and limitations of, opioid use for cancer-related pain, the identification of nonopioid treatment strategies that could improve cancer pain care is an attractive concept. The hypothesis that combinations of mechanistically distinct analgesic drugs could provide superior analgesia and/or fewer adverse effects has been tested in several pain conditions, including in cancer-related pain. Here, we propose to review trials of nonopioid analgesic combinations for cancer-related pain.Methods:Using a predefined literature search strategy, trials-comparing the combination of 2 or more nonopioid analgesics with at least one of the combination's individual components-will be searched on the PubMed and EMBASE databases from their inception until the date the searches are run. Outcomes will include pain intensity or relief, adverse effects, and concomitant opioid consumption.Results/Conclusions:This review is expected to synthesize available evidence describing the efficacy and safety of nonopioid analgesic combinations for cancer-related pain. Furthermore, a review of this literature will serve to identify future research goals that would advance our knowledge in this area.

Opioid misuse and overuse have contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five‐step modified Delphi process, we aimed to develop consensus‐based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids.

Background Computerized clinical decision support systems (CDSSs) have emerged as an approach to improve compliance of clinicians with clinical practice guidelines (CPGs). Research utilizing CDSS has primarily been conducted in clinical contexts with clear diagnostic criteria such as diabetes and cardiovascular diseases. In contrast, research on CDSS for pain management and more specifically neuropathic pain has been limited. A CDSS for neuropathic pain has the potential to enhance patient care as the challenge of diagnosing and treating neuropathic pain often leads to tension in clinician-patient relationships. Objective The aim of this study was to design and evaluate a CDSS aimed at improving the adherence of interprofessional primary care clinicians to CPG for managing neuropathic pain. Methods Recommendations from the Canadian CPGs informed the decision pathways. The development of the CDSS format and function involved participation of multiple stakeholders and end users in needs assessment and usability testing. Clinicians, including family medicine physicians, residents, and nurse practitioners, in three academic teaching clinics were trained in the use of the CDSS. Evaluation over one year included the measurement of utilization of the CDSS; change in reported awareness, agreement, and adoption of CPG recommendations; and change in the observed adherence to CPG recommendations. Results The usability testing of the CDSS was highly successful in the prototype environment. Deployment in the clinical setting was partially complete by the time of the study, with some limitations in the planned functionality. The study population had a high level of awareness, agreement, and adoption of guideline recommendations before implementation of CDSS. Nevertheless, there was a small and statistically significant improvement in the mean awareness and adoption scores over the year of observation (P=.01 for mean awareness scores at 6 and 12 months compared with baseline, for mean adoption scores at 6 months compared with baseline, and for mean adoption scores at 12 months). Documenting significant findings related to diagnosis of neuropathic pain increased significantly. Clinicians accessed CPG information more frequently than they utilized data entry functions. Nurse practitioners and first year family medicine trainees had higher utilization than physicians. Conclusions We observed a small increase in the adherence to CPG recommendations for managing neuropathic pain. Clinicians utilized the CDSS more as a source of knowledge and as a training tool than as an ongoing dynamic decision support.

Introduction Accumulating evidence has identified a number of advantages for methadone over other opioids for the treatment of chronic pain including: agonist action at both μ and δ opioid receptors, N-methyl-d-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines. It was hypothesized that with these three mechanisms of action methadone might be a good option for the treatment of neuropathic pain. Methods This was a double-blind randomized controlled trial comparing methadone to controlled-release morphine. The primary objective was to determine whether methadone is clinically inferior versus noninferior to morphine as an analgesic. Results We attempted recruitment at three academic pain centers over a 3-year period. In the end only 14 participants were able to be recruited; 5 withdrew and only 9 completed the trial. This study was underpowered. All participants showed a mean reduction in pain intensity according to the Numeric Rating Scale for Pain Intensity (morphine 5.86 to 4.38, methadone 6.11 to 4.5) and reported pain relief compared to pretreatment, but the sample size was too small for statistical analysis. Discussion Reasons for challenges in recruitment included tight inclusion and exclusion criteria and high participant burden. In addition, there was significant heterogeneity of patients between the three sites, leading to differences in reasons for exclusion. This included seemingly disparate reasons at the different sites, including few participants who were methadone naïve vs. avoidance or fear of opioids. In the end, we were unable to answer the question of the study.

OBJECTIVES:To determine if there are sex differences in a sample of patients participating in a 4-week interdisciplinary pain treatment program in (1) pretreatment pain intensity, physical function, psychological function, pain beliefs, kinesiophobia, pain catastrophizing, and activity management patterns; and (2) treatment response.METHODS:Seventy-two men and 130 women with chronic pain completed study measures. Analyses of covariance (ANCOVAs) were performed to compare men and women on pretreatment measures. Repeated-measures ANCOVAs were used to compare both sexes on 3 treatment outcomes (pain intensity, physical function, and depressive symptoms).RESULTS:Before treatment, compared to women, men reported higher levels of kinesiophobia, were more likely to view their pain as being harmful, and used more activity pacing when doing daily activities. Women were more likely to use an overdoing activity pattern than men. No sex differences emerged for pretreatment pain intensity, physical function, psychological function, catastrophizing, activity avoidance, or measures of other pain-related beliefs. At posttreatment, women reported more improvements in pain intensity and physical function compared to men, while both sexes reported similar reductions in depressive symptoms. All effect sizes for statistically significant findings were of small to moderate magnitude.DISCUSSION:The results of this study suggest that men and women have a comparable profile with respect to the overall burden of chronic pain. Nevertheless, sex differences were found for certain pain beliefs and coping styles. Women appear to reap more benefits from the interdisciplinary pain management program than men. These findings indicate that further research to develop sex-specific assessment procedures and tailored pain treatments may be warranted.

Neuropathic pain, resulting from injury to the peripheral or central nervous system, is due to upregulation of aberrant sodium channels with neuronal hyperexcitability. Lidocaine blocks these channels and several studies show that intravenous (IV) lidocaine infusion provides significant relief in patients with chronic peripheral neuropathic pain in the short term (for up to six hours). Our objective was to determine if IV lidocaine provides significant pain relief and overall improvement in quality of life in the longer term (for up to four weeks). This single site randomized double-blind, crossover trial compared IV lidocaine infusion (5 mg·kg−1) with active placebo infusion containing diphenhydramine (50 mg) in patients with chronic neuropathic pain of peripheral nerve origin of at least six months duration. The primary outcome was average pain intensity reduction from IV lidocaine relative to placebo at four weeks post-infusion. Secondary outcome measures included parameters of physical function, mood, and overall quality of life. We enrolled 34 subjects in this trial—mostly with painful diabetic neuropathy and post-herpetic neuralgia. There were no significant differences between IV lidocaine and placebo infusions at any time point involving any of the outcome measures. Mean (standard deviation) pain intensity at week 4 for the placebo and lidocaine groups were not different [6.58 (1.97) vs 6.78 (1.56), respectively; between-group difference, 0.17; 95% confidence interval, − 0.50 to 0.84]. We found no significant long-term analgesic or quality of life benefit from IV lidocaine relative to control infusion for chronic peripheral neuropathic pain. clinicaltrials.gov (NCT01669967); registered 22 June, 2012.

Objectives: To clarify the importance of avoidance, pacing, and overdoing pain-related activity management patterns as predictors of adjustment in patients with fibromyalgia syndrome. Methods: A total of 119 tertiary care patients with fibromyalgia syndrome who agreed to be part of an activity management pain program completed a survey, which requested information about demographics, pain intensity and pain interference, psychological and physical function, and pain-related activity management patterns. Hierarchical regression analyses were used to identify the unique contributions of the 3 different pain-related activity management patterns (avoidance, pacing, and overdoing) to the prediction of pain interference, psychological function, and physical function. Results: The avoidance pattern was a significant and unique predictor of worse psychological and physical function as well as greater pain interference. Pacing was significantly associated with less pain interference and better psychological function, whereas overdoing was not found to predict patient functioning. Discussion: The findings confirm the importance of pain-related activity management patterns as predictors of patient function, and support the necessity of addressing these factors in chronic pain treatment. In addition, the results suggest that targeting increases in activity pacing and decreases in pain avoidance, specifically, might yield the best patient outcomes. However, further research to evaluate this possibility is necessary.

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OBJECTIVES:Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes.MATERIALS AND METHODS:This prospective observational study was conducted in 7 Canadian academic pain centers between April 2008 and December 2011. All newly admitted patients (n=2199) were approached and 789 eligible participants form the sample for this analysis. Baseline data included demographics, disability, health-related quality of life, and pain characteristics. Diagnosis of probable or definite neuropathic pain was on the basis of history, neurological examination, and ancillary diagnostic tests.RESULTS:The mean age of study participants was 53.5 years and 54.7% were female; 83% (n=652/789) screened positive on the DN4 (≥4/10). The sensitivity was highest for central neuropathic pain (92.5%, n=74/80) and generalized polyneuropathies (92.1%, n=139/151), and lowest for trigeminal neuralgia (69.2%, n=36/52). After controlling for confounders, the sensitivity of the DN4 remained significantly higher for individuals with generalized polyneuropathies (odds ratio [OR]=4.35; 95% confidence interval [CI]: 2.15, 8.81), central neuropathic pain (OR=3.76; 95% CI: 1.56, 9.07), and multifocal polyneuropathies (OR=1.72; 95% CI: 1.03, 2.85) compared with focal neuropathies.DISCUSSION:The DN4 performed well; however, sensitivity varied by syndrome and the lowest sensitivity was found for trigeminal neuralgia. A positive DN4 was associated with greater pain catastrophizing, disability and anxiety/depression, which may be because of disease severity, and/or these scales may reflect magnification of sensory symptoms and findings. Future research should examine how the DN4 could be refined to improve its sensitivity for specific neuropathic pain conditions.