The Activity Management Inventory for Pain (AMI-P): Initial Development and Validation of a Questionnaire Based on Operant Learning and Energy Conservation Models of Activity Management.

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.

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial.

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.

Glial-modulating agents for the treatment of pain: protocol for a systematic review.

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.

Nonopioid drug combinations for cancer pain: a systematic review.

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.

The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

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.

Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process.

BACKGROUND: Globally, 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. METHODS: Using 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. RESULTS: There 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. CONCLUSIONS: In 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.

Risk of Chronic Opioid Use After Radiation for Head and Neck Cancer: A Systematic Review and Meta-Analysis.

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.

Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial.

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.

Consensus-based recommendations for titrating cannabinoids and tapering opioids for chronic pain control.

AIMS: 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. RESULTS: In patients with chronic pain taking opioids not reaching treatment goals, there was consensus that cannabinoids may be considered for patients experiencing or displaying opioid-related complications, despite psychological or physical interventions. There was consensus observed to initiate with a cannabidiol (CBD)-predominant oral extract in the daytime and consider adding tetrahydrocannabinol (THC). When adding THC, start with 0.5-3 mg, and increase by 1-2 mg once or twice weekly up to 30-40 mg/day. Initiate opioid tapering when the patient reports a minor/major improvement in function, seeks less as-needed medication to control pain and/or the cannabis dose has been optimised. The opioid tapering schedule may be 5%-10% of the morphine equivalent dose (MED) every 1 to 4 weeks. Clinical success could be defined by an improvement in function/quality of life, a ≥30% reduction in pain intensity, a ≥25% reduction in opioid dose, a reduction in opioid dose to <90 mg MED and/or reduction in opioid-related adverse events. CONCLUSIONS: This five-stage modified Delphi process led to the development of consensus-based recommendations surrounding the safe introduction and titration of cannabinoids in concert with tapering opioids.

Nonopioid drug combinations for cancer pain: protocol for a systematic review.

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.

An Evaluation of Sex Differences in Patients With Chronic Pain Undergoing an Interdisciplinary Pain Treatment Program.

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.

Pain-Related Activity Management Patterns as Predictors of Treatment Outcomes in Patients with Fibromyalgia Syndrome.

OBJECTIVES: This study sought to determine if pre- to post-treatment changes in pain-related activity patterns (i.e., overdoing, avoidance, and pacing) were associated with pre- to post-treatment changes in function (i.e., pain interference, psychological function, and physical function) in patients with fibromyalgia syndrome who participated in either an operant learning- or an energy conservation-based training in activity management. METHODS: Sixty-nine patients with fibromyalgia syndrome participated in an activity management treatment (32 in an operant learning group and 37 in an energy conservation group). Outcomes were assessed at pre- and post-treatment, and patients provided demographic information and completed measures assessing pain intensity, pain interference, psychological function, physical function, and pain management activity patterns. Three linear hierarchical regression analyses predicting changes in pain outcomes from changes in pacing, overdoing, and avoidant activity patterns were performed. RESULTS: Changes in pain-related activity patterns made significant contributions to the prediction of changes in patients' function. Specifically: (a) increases in overdoing predicted reductions in pain interference; (b) decreases in avoidance predicted improvements in psychological function; and (c) increases in pacing predicted improvements in physical function. CONCLUSIONS: This study provides support for a role of activity management treatments in improved adjustment to chronic pain. Research is needed to replicate and extend these findings in order to build an empirical basis for developing more effective chronic pain treatments for facilitating improved physical and psychological function in individuals with chronic pain.

Design Process and Utilization of a Novel Clinical Decision Support System for Neuropathic Pain in Primary Care: Mixed Methods Observational Study.

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.

Intravenous lidocaine in the management of chronic peripheral neuropathic pain: a randomized-controlled trial.

PURPOSE: 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). METHODS: 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. RESULTS: 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]. CONCLUSION: We found no significant long-term analgesic or quality of life benefit from IV lidocaine relative to control infusion for chronic peripheral neuropathic pain. TRIAL REGISTRATION: clinicaltrials.gov (NCT01669967); registered 22 June, 2012.

RéSUMé: OBJECTIF: La douleur neuropathique, résultat d'une lésion du système nerveux périphérique ou central, est due à l'augmentation de canaux sodiques aberrants accompagnée d'une hyperexcitabilité neuronale. La lidocaïne bloque ces canaux et plusieurs études ont démontré qu'une perfusion intraveineuse (IV) de lidocaïne offrait un important soulagement à court terme (pour une durée maximale de six heures) aux patients atteints de douleur neuropathique périphérique chronique. Notre objectif était de déterminer si la lidocaïne IV procurait un soulagement significatif de la douleur et une amélioration globale de la qualité de vie à plus long terme (pour une durée maximale de quatre semaines). MéTHODE: Cette étude randomisée croisée à double insu et mono-site a comparé une perfusion de lidocaïne IV (5 mg·kg−1) à une perfusion de placebo actif contenant de la diphenhydramine (50 mg) chez des patients atteints de douleur neuropathique chronique provenant du système nerveux périphérique et durant depuis au moins six mois. Le critère d'évaluation principal était la réduction moyenne de l'intensité de la douleur procurée par la lidocaïne IV par rapport au placebo à quatre semaines post-perfusion. Les critères d'évaluation secondaires comprenaient divers paramètres pour mesurer la capacité physique fonctionnelle, l'humeur et la qualité de vie globale. RéSULTATS: Nous avons recruté 34 patients pour cette étude, la plupart souffrant de neuropathie diabétique douloureuse et de névralgie post-herpétique. Aucune différence significative n'a été observée entre les perfusions de lidocaïne IV et de placebo, quel que soit le point de mesure dans le temps, pour aucun de nos critères d'évaluation. L'intensité de la douleur moyenne (écart type) à la semaine 4 était similaire dans les groupes placebo et lidocaïne [6,58 (1,97) vs 6,78 (1,56), respectivement; différence intergroupe, 0,17; intervalle de confiance 95 %, − 0,50 à 0,84]. CONCLUSION: Nous n'avons trouvé aucun bienfait significatif sur l'analgésie à long terme ou la qualité de vie d'une perfusion de lidocaïne IV par rapport à une perfusion témoin pour soulager la douleur neuropathique périphérique chronique. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT01669967); enregistrée le 22 juin 2012.

Long-Term Outcomes in the Management of Central Neuropathic Pain Syndromes: A Prospective Observational Cohort Study.

BACKGROUND: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. METHODS: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. RESULTS: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). CONCLUSION: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes.

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.

Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome.

Brain plasticity is demonstrated in complex regional pain syndrome (CRPS), although it is unclear how it modulates at different stages of CRPS. The observation that symptoms can progress over time suggests that the pattern of brain changes might also evolve. We measured structural and functional changes as well as sensorimotor integration at the early stage (ES) and late stage (LS) of CRPS. Twelve ES patients, 16 LS patients, and 16 age- and sex-matched controls were recruited. Gray matter (GM) volume was estimated using voxel-based morphometry. Cerebral perfusion was measured using arterial spin labeling, because it provides a measure of resting neural activity. Connectivity to sensorimotor regions was evaluated using blood-oxygen level-dependent images. The ES group showed reduced GM volume and perfusion in areas associated with spatial body perception, somatosensory cortex, and the limbic system, whereas the LS group exhibited increased perfusion in the motor cortex but no changes in GM volume. However, in the LS group, GM volume in areas associated with pain processing was negatively correlated with average pain levels, likely reflecting a response to ongoing pain. Furthermore, connectivity to sensorimotor cortex showed disruptions in regions associated with motor control and planning, implying impairment of higher-order motor control. PERSPECTIVE: This article presents brain changes at ES and LS of CRPS. We found different patterns of brain changes between these 2 stages. Understanding modulation of brain plasticity at different stages of CRPS could help understand the diversity in outcomes and treatment response and hopefully improve treatment planning.

Pain-related Activity Management Patterns and Function in Patients With Fibromyalgia Syndrome.

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.

Pharmacologic management of chronic neuropathic pain: Review of the Canadian Pain Society consensus statement.

OBJECTIVE: To provide family physicians with a practical clinical summary of the Canadian Pain Society (CPS) revised consensus statement on the pharmacologic management of neuropathic pain. QUALITY OF EVIDENCE: A multidisciplinary interest group within the CPS conducted a systematic review of the literature on the current treatments of neuropathic pain in drafting the revised consensus statement. MAIN MESSAGE: Gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are the first-line agents for treating neuropathic pain. Tramadol and other opioids are recommended as second-line agents, while cannabinoids are newly recommended as third-line agents. Other anticonvulsants, methadone, tapentadol, topical lidocaine, and botulinum toxin are recommended as fourth-line agents. CONCLUSION: Many pharmacologic analgesics exist for the treatment of neuropathic pain. Through evidence-based recommendations, the CPS revised consensus statement helps guide family physicians in the management of patients with neuropathic pain.