Pain
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Review Meta Analysis
Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies.
This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to identify important directions for future research. ⋯ Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.
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We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. ⋯ The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
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Cannabinoids, cannabis, and cannabis-based medicines (CBM) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We assessed methodological quality, scope, and results of systematic reviews of randomised controlled trials of these treatments. Several search strategies sought self-declared systematic reviews. ⋯ Systematic reviews with positive or negative recommendation for use of cannabinoids, cannabis, or CBM in pain typically rated critically low or low (24/25 [96%] positive; 10/12 [83%] negative). Current reviews are mostly lacking in quality and cannot provide a basis for decision-making. A new high-quality systematic review of randomised controlled trials is needed to critically assess the clinical evidence for cannabinoids, cannabis, or CBM in pain.
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The management of acute postoperative pain remains suboptimal. Systematic reviews and Cochrane analysis can assist with collating evidence about treatment efficacy, but the results are limited in part by heterogeneity of endpoints in clinical trials. In addition, the chosen endpoints may not be entirely clinically relevant. ⋯ In conclusion, we found that there was high variability in outcome domains and inhomogeneous combinations, as well as inconsistent subdomain descriptions and utilization in trials comparing for effectiveness of pain interventions after total knee arthroplasty. This points towards the need for harmonizing outcome domains, eg, by consenting on a core outcome set of domains which are relevant for both stakeholders and patients. Such a core outcome set should include at least 3 domains from 3 different health core areas such as pain intensity, physical function, and one psychological domain.
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Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). ⋯ This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines.