Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies.

Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon. Five recent pre-clinical studies identified from Medline published between 2013 and 2016 were selected for review. All studies evaluated the effect of small-molecule agonists or antagonists on components of the endocannabinoid system in rats or mice, using cisplatin or paclitax-el-induced allodynia as a model of chemotherapy-induced neuropathic pain. Activation of the cannabinoid receptor-2 (CB-2) receptor by AM1710 blocked paclitaxel-induced mechanical and cold allodynia in one study. Four studies investigating the activation of both cannabinoid receptor-1 (CB-1) and CB-2 receptors by dual-agonists (WIN55,21 and CP55,940), or by the introduction of inhibitors of endocannabinoid metabolisers (URB597, URB937, JZL184, and SA-57) showed reduction of chemotherapy-induced al-lodynia. In addition, their results suggest that anti-allodynic effects may also be mediated by additional receptors, including TRPV1 and 5-hydroxytryptamine (5-HT1A). Pre-clinical studies demon-strate that the activation of endocannabinoid CB-1 or CB-2 receptors produces physiological effects in animal models, namely the reduction of chemotherapy-induced allodynia. These studies also provide in-sight into the biological mechanism behind the therapeutic utility of cannabis compounds in managing chemotherapy-induced neuropathic pain, and provide a basis for the conduct of future clinical studies in patients of this population.

Does gender affect self-perceived pain in cancer patients? -A meta-analysis.

BACKGROUND: Pain is reported in approximately 50-70% of cancer patients. Studies on gender differences in perceived pain generally report lower pain thresholds and increased pain prevalence in women, which may be attributed to gender-specific behaviors, stereotypes, and unknown etiological factors. There are sparse and inconclusive results on gender differences in self-perceived pain in the cancer setting. The aim of this article was to examine the effect of gender on baseline perceived pain intensity in cancer patients through a meta-analysis. METHODS: A literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1947-2016] to identify observational studies and controlled trials that reported on gender-specific pain intensity in cancer patients. Using random-effects modeling, weighted mean differences and 95% confidence intervals (CI) were used to estimate the effect of gender on pain severity in cancer patients. A P value of less than 0.05 was considered statistically significant. RESULTS: Of the 1,911 search results reviewed, 13 studies were included. The weighted mean difference (95% CI) in pain intensity was as follows: -0.26 (95% CI: -0.57 to 0.04, P=0.09) for the 0-10 Numerical Rating Scale (NRS) group (n=3,752, 9 studies). When restricted to only patients with advanced cancer, the weighted mean difference was -0.08 (95% CI: -0.36 to 0.20, P=0.58) (n=2,762, 4 studies). The weighted mean difference in the Brief Pain Inventory scores between males and females was 0.03 (95% CI: -1.23 to 1.29, P=0.96) (n=521, 4 studies). CONCLUSIONS: Baseline perceived pain intensity in cancer patients did not significantly differ based on gender.

A selective review of medical cannabis in cancer pain management.

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.