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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Residual limb pain (RLP) is associated with (partial) extremity amputations and is defined as pain felt in the remaining part of the amputated limb. A common cause of RLP is neuroma formation after nerve transections. Neuromas can be very painful and severely debilitating pathologies, preventing prosthetic use, reducing quality of life, and requiring medication. ⋯ Residual limb pain subgroup analysis showed statistically significant higher prevalence in patients aged >50 years, follow-up >2 years, and in studies using a self-administered questionnaire for data collection. The prevalence of RLP and symptomatic neuroma in patients who have had a lower extremity amputation is 59% and 15%, respectively. Knowledge of their high prevalence may result in better awareness among physicians, in turn providing timely and adequate management.
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Meta Analysis
Prognostic factors for adolescent knee pain: an individual participant data meta-analysis of 1281 patients.
Adolescent knee pain has a propensity for chronicity, impacting physical activity and health into adulthood. The aim of this study is to investigate prognostic factors in adolescents with knee pain using individual participant data (IPD) meta-analysis. Studies were identified through a systematic search and a collaborative group. ⋯ Body mass index, pain sensitivity, and knee strength were not associated with prognosis of pain or function. Adolescent knee pain is associated with clinically relevant long-term pain and functional deficits. Self-reported characteristics may help identify those at risk of poor prognosis.
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Meta Analysis
Long-term inflammatory pain does not impact exploratory behavior and stress coping strategies in mice.
Pain puts patients at risk for developing psychiatric conditions such as anxiety and depression. Preclinical mouse models of pain-induced affective behavior vary widely in methodology and results, impairing progress towards improved therapeutics. To systematically investigate the effect of long-term inflammatory pain on exploratory behavior and stress coping strategy, we assessed male C57BL/6J mice in the forced swim test (FST), elevated zero maze, and open field test at 4 and 6 weeks postinjection of Complete Freund's Adjuvant, while controlling for testing order and combination. ⋯ A meta-analysis of similar studies indicated a modest, significant effect of Complete Freund's Adjuvant on exploratory behavior, but not immobility in the FST, and high heterogeneity among effect sizes in all 3 paradigms. Given the urgency for understanding the mechanisms of pain comorbidities and identifying novel therapies, these findings support the reallocation of our limited resources away from such unreliable assays and toward motivated and naturalistic behaviors. Future studies in pain and psychiatric translational research may benefit by considering outcomes beyond binary categorization, quantifying the associations between multiple measured behaviors, and agnostically identifying subtle yet meaningful patterns in behaviors.