Pain Research, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, Missouri, United States.
Pain. 2021 Jul 1;162(Suppl 1):S26-S44. doi: 10.1097/j.pain.0000000000002269.
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. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. 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.
我们报告了一项系统评价和荟萃分析，评估了大麻素、基于大麻的药物和内源性大麻素系统调节剂在病理性或损伤相关性持续性疼痛动物模型中对疼痛相关行为结果的抗伤害作用。2019 年 4 月，我们系统地检索了 3 个在线数据库，并利用众包科学和机器学习来识别纳入研究。我们为每一次比较计算了标准化均数差值效应大小，并进行了随机效应荟萃分析。我们评估了研究设计特征和减轻偏倚风险报告的影响。我们对 374 项研究进行了荟萃分析，其中 171 项干预措施在病理性或损伤相关性疼痛的啮齿动物模型中评估了抗伤害作用。大多数实验都是在雄性动物中进行的（86%）。抗伤害作用最常通过减轻对诱发肢体退缩的过敏反应来测量。选择性大麻素 1 型、大麻素 2 型、非选择性大麻素受体激动剂（包括 δ-9-四氢大麻酚）和过氧化物酶体增殖物激活受体-α激动剂（主要是棕榈酸乙醇酰胺）在广泛的炎症和神经病理性疼痛模型中显著减轻了与疼痛相关的行为。脂肪酸酰胺水解酶抑制剂、单酰基甘油脂肪酶抑制剂和大麻二酚在神经病理性疼痛模型中显著减轻了与疼痛相关的行为，但在炎症性疼痛模型中结果不一致。减少偏倚风险标准的报告率较低；因此，这些研究的偏倚风险不明确。通过提高方法学标准、模型的临床相关性和行为评估的报告，可以提高未来研究的价值。尽管如此，证据支持大麻素诱导镇痛的假说。
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