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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.

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED 50 ) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED 50 of morphine alone. In addition, the ED 50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED 50 of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.

Unlabelled: Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%., Perspective: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: We have examined the characteristics of the pain experience as well as barriers to optimal pain management in 60 patients with rheumatoid arthritis (RA) consecutively attending a specialist rheumatology practice. Pain was reported to be moderate to severe in 32 (53%) and mild to absent in 28 (47%). Sixty-five percent of all patients, including almost half of those with moderate to severe pain, reported satisfaction with current pain control. The average number of barriers to pain management for individual patients was 2.6 +/- 1.5, with 33 patients (55%) reporting 3 or more barriers. Specific barriers included concern about side effects of medications in 80%, dislike for "too many pills" in 63%, concern about drug interactions in 57%, fear of addiction in 35%, and fear of masking disease in 27% of the patients. More barriers were significantly associated with higher pain level (r = .33, P = .011) and pain intensity on a visual analogue scale (r = .29, P = .024). Other than the regular use of nonsteroidal anti-inflammatory drugs in 37% of the patients and acetaminophen in 37%, analgesics or other modalities to reduce pain were seldom used., Perspective: Moderate to severe pain was present in over half of patients with RA with many reporting the presence of considerable barriers to pain control. These barriers likely contribute to sub optimal pain management. RA patients tolerate pain and use limited mechanisms to deal with the symptom of pain.

Background: The therapeutic use of cannabis and cannabis-based medicines raises safety concerns for patients, clinicians, policy-makers, insurers, researchers and regulators. Although the efficacy of cannabinoids is being increasingly demonstrated in randomized controlled trials, most safety information comes from studies of recreational use., Methods: We performed a systematic review of safety studies of medical cannabinoids published over the past 40 years to create an evidence base for cannabis-related adverse events and to facilitate future cannabis research initiatives. We critically evaluated the quality of published studies with a view to identifying ways to improve future studies., Results: A total of 321 articles were eligible for evaluation. After excluding those that focused on recreational cannabis use, we included 31 studies (23 randomized controlled trials and 8 observational studies) of medical cannabis use in our analysis. In the 23 randomized controlled trials, the median duration of cannabinoid exposure was 2 weeks (range 8 hours to 12 months). A total of 4779 adverse events were reported among participants assigned to the intervention. Most (4615 [96.6%]) were not serious. Of the 164 serious adverse events, the most common was relapse of multiple sclerosis (21 events [12.8%]), vomiting (16 events [9.8%]) and urinary tract infection (15 events [9.1%]). The rate of nonserious adverse events was higher among participants assigned to medical cannabinoids than among controls (rate ratio [RR] 1.86, 95% confidence interval [CI] 1.57-2.21); the rates of serious adverse events did not differ significantly between these 2 groups (RR 1.04, 95% CI 0.78-1.39). Dizziness was the most commonly reported nonserious adverse event (714 events [15.5%]) among people exposed to cannabinoids., Interpretation: Short-term use of existing medical cannabinoids appeared to increase the risk of nonserious adverse events. The risks associated with long-term use were poorly characterized in published clinical trials and observational studies. High-quality trials of long-term exposure are required to further characterize safety issues related to the use of medical cannabinoids.

Unlabelled: Certain dietary proteins and oils are capable of decreasing chronic neuropathic pain levels in rats after partial sciatic nerve ligation injury. We tested, for the first time, the role of dietary polyunsaturated fatty acids in suppressing pain in partial sciatic nerve ligation-injured rats. Six groups of male Wistar rats were fed an identical casein-based, fat-free diet for 1 wk preceding partial sciatic nerve ligation injury and for 1 wk thereafter. In addition, rats received, via gavage, 1 mL/day of pure canola, corn, hemp, soy, or sunflower oil, differing significantly in their omega-3 and omega-6 polyunsaturated fatty acid content, or 1 mL of plain water. Responses to tactile and noxious heat stimuli were recorded before and after surgery and a difference score was calculated for each group by subtracting the preoperative from the post-partial sciatic nerve ligation values. Heat hyperalgesia, but not tactile allodynia, was significantly different among the dietary groups (P = 0.005). Heat hyperalgesia of rats fed hemp oil, developing the most robust response, was significantly larger compared with rats fed corn oil, developing the least pain model (difference score: 24.3 +/- 4.1 s versus 6.1 +/- 3.1 s, respectively; P < 0.001). These oils contain similar levels of omega-6 polyunsaturated fatty acids (hemp, 60%; corn, 58%) but their omega-3 levels are 28-fold different (20% versus 0.7%, respectively). A significant correlation was found among dietary levels of omega-3, but not omega-6 or the omega-3/omega-6 ratio, of the six dietary groups and heat hyperalgesia (P = 0.006). We conclude that dietary oil might predict levels of neuropathic pain in rats and that this effect may be associated with dietary omega-3 levels., Implications: We found that certain commonly used oils can have a significant analgesic effect in rats with persistent pain after partial nerve injury. This effect may be associated with the amounts of omega-3 fatty acids consumed by rats.

Chronic neuropathic sensory disorders (CNSD) of rats receiving a partial sciatic nerve ligation injury (the PSL model) are suppressed by dietary soy protein. Although previously shown to modify nociceptive behavior in acute pain models, dietary fat has never been tested for its putative analgesic properties in chronic pain states. Here we tested the role of dietary fat, protein and fat/protein interactions in the development of tactile allodynia and heat hyperalgesia in PSL-injured rats. Male Wistar rats were fed nine different diets, comprising of three proteins (soy, casein and albumin) and three fats (corn, soy and canola) for a week preceding PSL injury and for 2 weeks thereafter. Rats' responses to tactile and noxious heat stimuli were tested before surgery and 3, 7 and 14 days afterwards. Tactile and heat sensory abnormalities following PSL injury were significantly different among the nine dietary groups. Consumption of corn and soy fats suppressed the levels of tactile and heat allodynia and hyperalgesia, whereas consumption of soy and casein proteins was associated with lower levels of heat hyperalgesia but not tactile allodynia. A significant fat/protein interaction was found for the heat but not tactile stimuli. We conclude that dietary fat is a significant independent predictor of levels of neuropathic sensory disorders in rats and that this effect is accentuated by dietary protein. The mechanisms by which fat suppresses neuropathic disorders have yet to be determined.

There has been a surge in interest in medicinal cannabis in Canada. We conducted a questionnaire survey to determine the current prevalence of medicinal cannabis use among patients with chronic non-cancer pain, to estimate the dose size and frequency of cannabis use, and to describe the main symptoms for which relief was being sought. Over a 6-week period in mid-2001, 209 chronic non-cancer pain patients were recruited in an anonymous cross-sectional survey. Seventy-two (35%) subjects reported ever having used cannabis. Thirty-two (15%) subjects reported having used cannabis for pain relief (pain users), and 20 (10%) subjects were currently using cannabis for pain relief. Thirty-eight subjects denied using cannabis for pain relief (recreational users). Compared to never users, pain users were significantly younger (P=0.001) and were more likely to be tobacco users (P=0.0001). The largest group of patients using cannabis had pain caused by trauma and/or surgery (51%), and the site of pain was predominantly neck/upper body and myofascial (68% and 65%, respectively). The median duration of pain was similar in both pain users and recreational users (8 vs. 7 years; P=0.7). There was a wide range of amounts and frequency of cannabis use. Of the 32 subjects who used cannabis for pain, 17 (53%) used four puffs or less at each dosing interval, eight (25%) smoked a whole cannabis cigarette (joint) and four (12%) smoked more than one joint. Seven (22%) of these subjects used cannabis more than once daily, five (16%) used it daily, eight (25%) used it weekly and nine (28%) used it rarely. Pain, sleep and mood were most frequently reported as improving with cannabis use, and 'high' and dry mouth were the most commonly reported side effects. We conclude that cannabis use is prevalent among the chronic non-cancer pain population, for a wide range of symptoms, with considerable variability in the amounts used. Discussions between patients and health care providers concerning cannabis use may facilitate education and follow up, and would allow side effects and potential interactions with other medications to be monitored. Clinical trials of cannabis for chronic non-cancer pain are warranted.

Background: Chronic pain is one of the most common reasons for therapeutic cannabis use., Objectives: To describe therapeutic cannabis use among patients with chronic pain., Methods: Patients with chronic pain who voluntarily indicated that they used cannabis therapeutically completed a questionnaire about the type of cannabis used, the mode of administration, the amount used and the frequency of use, and their perception of the effectiveness of cannabis on a set of pain-associated symptoms and side effects. The study was approved by the McGill University Health Centre Research Ethics Board., Results: Fifteen patients (10 male) were interviewed (median age 49.5 years, range 24 to 68 years). All patients smoked herbal cannabis for therapeutic reasons (median duration of use six years, range two weeks to 37 years). Seven patients only smoked at night-time (median dose eight puffs, range two to eight puffs), and eight patients used cannabis mainly during the day (median dose three puffs, range two to eight puffs); the median frequency of use was four times per day (range one to 16 times per day). Twelve patients reported improvement in pain and mood, while 11 reported improvement in sleep. Eight patients reported a 'high'; six denied a 'high'. Tolerance to cannabis was not reported., Conclusions: The results of this self-selected case series must be interpreted with caution. Small doses of smoked cannabis may improve pain, mood and sleep in some patients with chronic pain. Clinical trials are warranted to test these effects. Further prospective studies should examine the patterns and prevalence of cannabis use among chronic pain populations.

BACKGROUND:Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS:This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS:We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Objective: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co‐occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. Methods: This was a 12‐month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow‐up assessment visits occurred every 3 months after initiation of medical cannabis. Patients' levels of pain intensity, negative affect, and sleep problems were assessed across all visits. Results: Multilevel mediation analyses indicated that reductions in patients' levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients' baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). Conclusion: Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis. [ABSTRACT FROM AUTHOR]

Objective: Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed. Data Sources: A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored. Main Results: Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug. Conclusions: Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention. [ABSTRACT FROM AUTHOR]

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The article presents a study conducted by the authors related to off-label use of pregabalin by pain patients. Topics discussed include the use of pregabalin mostly for lumbar back pain, discontinuing its use due to weight gain and dry mouth, no difference between affect of on-label and off-label pregabalin use on quality of life and dry m majority of patients using it for off-label conditions.

Aim Nabilone is a synthetic cannabinoid prescription drug approved in Canada since 1981 to treat chemotherapy-induced nausea and vomiting. In recent years, off-label use of nabilone for chronic pain management has increased, and physicians have begun to express concerns about nabilone becoming a drug of abuse. This study evaluates the evidence for abuse of nabilone, which is currently ill-defined. Study design Scientific literature, popular press and internet databases were searched extensively for evidence of nabilone abuse. Focused interviews with medical professionals and law enforcement agencies across Canada were also conducted. Findings The scientific literature and popular press reviews found very little reference to nabilone abuse. Nabilone is perceived to produce more undesirable side effects, to have a longer onset of action and to be more expensive than smoked cannabis. The internet review revealed rare and isolated instances of recreational use of nabilone. The database review yielded little evidence of nabilone abuse, although nabilone seizures and thefts have occurred in Canada in the past few years, especially in Ontario. Most law enforcement officers reported no instances of nabilone abuse or diversion, and the drug has no known street value. Medical professionals reported that nabilone is not perceived to be a matter of concern with respect to its abuse potential. Conclusions Reports of nabilone abuse are extremely rare. However, follow-up of patients using nabilone for therapeutic purposes is prudent and should include assessment of tolerance and dependence. Prospective studies are also needed to definitively address the issue of nabilone abuse. [ABSTRACT FROM AUTHOR]