Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, 201908, China.
Neuropharmacology. 2021 May 15;189:108515. doi: 10.1016/j.neuropharm.2021.108515. Epub 2021 Mar 17.
Patients deprived of cigarettes exhibit increased pain sensitivity during perioperative periods, yet the underlying neuroanatomical and molecular bases of this hypersensitivity are unclear. The present study showed that both the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were significantly decreased in a rat model of nicotine withdrawal. These rats showed less tryptophan hydroxylase 2 (TPH2) positive neurons and reduced TPH2 expression in the nucleus raphe magnus (NRM), and thus resulted in decreased 5-hydroxytryptamine (5-HT) levels in cerebrospinal fluid. Intrathecal injection of 5-HT or NRM microinjection of TPH-overexpression adeno-associated virus alleviated nicotine withdrawal-induced hyperalgesia, whereas 5-HT receptor pharmacological blockade by methysergide (a 5-HT receptor antagonist) exacerbated hypersensitivity and diminished the difference between the two groups. Together, these data indicate that hyperalgesia after nicotine withdrawal is mediated by declined descending serotonergic pathways in the NRM. This provides a new perspective to improve the postoperative pain management of patients, especially the smokers.
在围手术期，被剥夺香烟的患者表现出疼痛敏感性增加，但这种超敏反应的潜在神经解剖学和分子基础尚不清楚。本研究表明，在尼古丁戒断的大鼠模型中，机械撤回阈值 (MWT) 和热撤回潜伏期 (TWL) 均显著降低。这些大鼠显示出更少的色氨酸羟化酶 2 (TPH2) 阳性神经元和中缝大核 (NRM) 中 TPH2 表达减少，从而导致脑脊液中 5-羟色胺 (5-HT) 水平降低。鞘内注射 5-HT 或 NRM 中 TPH 过表达腺相关病毒的微注射缓解了尼古丁戒断引起的痛觉过敏，而用麦角乙脲（5-HT 受体拮抗剂）进行 5-HT 受体药理学阻断则加剧了过敏反应，并缩小了两组之间的差异。总之，这些数据表明，尼古丁戒断后的痛觉过敏是由 NRM 中下降的下行 5-羟色胺能途径介导的。这为改善患者（尤其是吸烟者）的术后疼痛管理提供了新的视角。
