Bade Sahil, Hurdle Mark Friedrich B, Bade Sohail, Encalada Sebastian, Kanahan-Osman Sharima, Gupta Sahil
Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.
Department of Pain Medicine, Mayo Clinic, Jacksonville, FL, USA.
Pain Manag. 2025 Jul 28:1-13. doi: 10.1080/17581869.2025.2536998.
Chronic pain imposes a significant healthcare burden, with treatments often limited by side effects, opioid dependency, and preventable surgeries. Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for diabetes and obesity, may offer novel analgesia and treat drug-seeking behavior. This review examines the role of GLP-1RAs in pain management, focusing on inflammation, macrophage repolarization, oxidative stress, and dopaminergic pathways in substance use disorders. We conducted a literature search in PubMed and Embase (Ovid) from January 2000 to February 2025, identifying studies on GLP-1RA and pain in headaches, osteoarthritis, diabetic neuropathy, and substance use disorders. GLP-1RAs offer a promising shift in pain management, potentially reducing opioid dependence, preventing surgical interventions, and lowering healthcare costs. While early evidence suggests analgesic and disease-modifying effects beyond weight loss, significant knowledge gaps remain. In osteoarthritis, they appear to reduce inflammation and cartilage degradation, but trials in non-obese, non-comorbid patients are needed. In diabetic neuropathy, GLP-1RAs show potential for nerve repair, but optimal dosing and long-term efficacy need clarification. Preclinical data support GLP-1RAs signaling in migraines, but human studies are lacking. Trials in alcohol addiction show promise, though evidence for other substances remains inconclusive. Larger-scale trials are needed to confirm these findings.
慢性疼痛带来了巨大的医疗负担，其治疗往往受到副作用、阿片类药物依赖和可避免的手术的限制。新出现的证据表明，为糖尿病和肥胖症开发的胰高血糖素样肽-1受体激动剂（GLP-1RAs）可能提供新的镇痛作用并治疗药物成瘾行为。本综述探讨了GLP-1RAs在疼痛管理中的作用，重点关注物质使用障碍中的炎症、巨噬细胞重极化、氧化应激和多巴胺能途径。我们在2000年1月至2025年2月期间在PubMed和Embase（Ovid）上进行了文献检索，确定了关于GLP-1RA与头痛、骨关节炎、糖尿病性神经病变和物质使用障碍疼痛的研究。GLP-1RAs在疼痛管理方面提供了一个有前景的转变，有可能减少阿片类药物依赖、避免手术干预并降低医疗成本。虽然早期证据表明其具有超出体重减轻的镇痛和疾病改善作用，但仍存在重大知识空白。在骨关节炎中，它们似乎能减轻炎症和软骨降解，但需要在非肥胖、无合并症的患者中进行试验。在糖尿病性神经病变中，GLP-1RAs显示出神经修复的潜力，但最佳剂量和长期疗效需要进一步明确。临床前数据支持GLP-1RAs在偏头痛中的信号传导，但缺乏人体研究。酒精成瘾试验显示出前景，不过其他物质的证据仍不确定。需要更大规模的试验来证实这些发现。
