Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Project to end Opioid Misuse, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
J Pain. 2023 Jul;24(7):1262-1274. doi: 10.1016/j.jpain.2023.02.024. Epub 2023 Mar 1.
Approximately half of patients with alcohol use disorder report pain and this can be severe during withdrawal. Many questions remain regarding the importance of biological sex, alcohol exposure paradigm, and stimulus modality to the severity of alcohol withdrawal-induced hyperalgesia. To examine the impact of sex and blood alcohol concentration on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of chronic alcohol withdrawal-induced pain in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor ± pyrazole exposure for 4 weeks, 4 d/wk to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hours after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of chronic intermittent ethanol vapor exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that Chronic alcohol withdrawal-induced pain develops in a sex-, time-, and blood alcohol concentration-dependent manner in C57BL/6J mice. PERSPECTIVE: Alcohol withdrawal-induced pain is a debilitating condition in individuals with AUD. Our study found mice experience alcohol withdrawal-induced pain in a sex and time course specific manor. These findings will aid in elucidating mechanisms of chronic pain and AUD and will help individuals remain abstinent from alcohol.
大约一半的酒精使用障碍患者报告有疼痛，并且在戒断期间可能会非常严重。关于生物性别、酒精暴露范式和刺激方式对酒精戒断引起的痛觉过敏的严重程度的重要性，仍有许多问题尚未解决。为了研究性别和血酒精浓度对机械性和热痛觉过敏发展时间过程的影响，我们在存在或不存在乙醇脱氢酶抑制剂吡唑的情况下，对慢性酒精戒断引起的疼痛的小鼠模型进行了表征。雄性和雌性 C57BL/6J 小鼠接受慢性间歇性乙醇蒸气±吡唑暴露 4 周，每周 4 天，以诱导乙醇依赖。在停止乙醇暴露后 1、3、5、7、24 和 48 小时每周观察时，测量后爪对足底应用机械（von Frey 纤维）和辐射热刺激的敏感性。在吡唑存在的情况下，雄性在慢性间歇性乙醇蒸气暴露的第一周后出现机械性痛觉过敏，在停止乙醇后 48 小时达到高峰。相比之下，雌性直到第四周才出现机械性痛觉过敏；这也需要吡唑，并且直到 48 小时才达到高峰。只有暴露于乙醇和吡唑的雌性才会持续观察到热痛觉过敏；这在第一周的会议后发展，并在 1 小时达到高峰。我们得出结论，慢性酒精戒断引起的疼痛在 C57BL/6J 小鼠中以性别、时间和血酒精浓度依赖的方式发展。观点：酒精戒断引起的疼痛是 AUD 患者衰弱的一种状况。我们的研究发现，小鼠在特定的性别和时间过程中经历酒精戒断引起的疼痛。这些发现将有助于阐明慢性疼痛和 AUD 的机制，并帮助个体保持戒酒。
