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前扣带皮层5-HT_1A受体介导电针缓解大鼠痛情绪

申杰^1,2, 王凯妮¹, 高洁¹, 石宇¹, 毕涛然¹, 赵欣¹, 张宇^1,*

¹山西医科大学生理学系暨细胞生理学教育部重点实验室，太原 030001；²太原钢铁(集团)有限公司总医院(山西医科大学第六医院)，太原 030001

摘要

本研究旨在探究前扣带皮层(anterior cingulate cortex, ACC) 5-羟色胺1A (5-hydroxytryptamine 1A , 5-HT1A)受体在电针缓解大鼠痛情绪中的作用。首先在随机分组大鼠的双侧ACC分别微量注射生理盐水、5-HT1A受体激动剂8-OH-DPAT 或5-HT1A受体抑制剂WAY-100635，随后在大鼠左后足掌皮下给予完全弗氏佐剂(complete Freund's adjuvant, CFA)建立慢性炎性痛模型，并与特定环境匹配形成条件位置逃避(conditioned place avoidance, CPA)反应，此后用电针刺激(10 Hz, 3 mA)大鼠环跳穴(GB30)，电针后同步观察大鼠在疼痛环境中的CPA反应与ACC脑区神经元的放电活动，最后进行旷场行为、热缩足反射潜伏期(paw withdrawal latency, PWL)和50%机械缩足阈值(paw withdrawal threshold, PWT)测试。结果显示：(1)与对照组相比，左后足掌皮下注射CFA的大鼠PWL与50% PWT明显降低(P < 0.05)，在“疼痛环境”和旷场中心的停留时间明显缩短(P < 0.05)；(2)免疫荧光双标结果显示，普通大鼠只给予电针刺激后，ACC脑区Fos 蛋白与5-HT1A受体高度共表达；(3)预先在ACC注射8-OH-DPAT (8 μg)可缓解CFA所致的痛情绪反应(P < 0.05)，并翻转CFA诱发的ACC脑区锥体神经元放电频率的增加(P < 0.05)；(4)预先在ACC注射WAY-100635 (8 μg)并给予电针刺激，可以翻转电针缓解CFA诱导大鼠的CPA样行为反应，且ACC脑区锥体神经元放电频率增加(P < 0.05)。上述结果表明，ACC脑区的5-HT1A受体介导了电针缓解CFA诱导的大鼠痛情绪。

关键词： 前扣带皮层; 痛情绪; 5-HT1A受体; 电针; 在体多通道电生理

5-HT_1A receptors in the anterior cingulate cortex mediate electroacupuncture to alleviate the affective pain in rats

SHEN Jie^1,2, WANG Kai-Ni¹, GAO Jie¹, SHI Yu¹, BI Tao-Ran¹, ZHAO Xin¹, ZHANG Yu^1,*

¹Department of Physiology and Key Laboratory of Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China；²General Hospital of Tisco, Sixth Hospital of Shanxi Medical University, Taiyuan 030001, China

Abstract

This study aimed to investigate the role of 5-hydroxytryptamine 1A (5-HT1A) receptors in the anterior cingulate cortex (ACC) in regulating the affective pain in rats. In the ACC, normal saline (NS), the 5-HT1A receptor agonist 8-OH-DPAT or the 5-HT1A receptor antagonist WAY-100635 was pre-injected respectively. A persistent inflammatory pain model was established by subcutaneously injecting 0.08 mL of complete Freund's adjuvant (CFA) into the left hind paw of rats, which was then paired with a specific environment to induce a conditioned place avoidance (CPA) response. Then the electroacupuncture (EA, 10 Hz, 3 mA) was applied to stimulate the Huantiao acupoint (GB30). The CPA responses of rats in the pain-paired environment and the firing activities of ACC neurons were simultaneously observed. Subsequently, open-field behavior, paw withdrawal latency (PWL), and 50% paw withdrawal threshold (PWT) tests were conducted. The results showed that: (1) Rats injected with CFA showed significant reductions in PWL and 50% PWT, and spent less time in the "pain-paired environment" and the center of the open field, compared to the control group (P < 0.05). (2) Immunofluorescence double-labeling results showed a high co-expression of Fos protein and 5-HT1A receptors in the ACC of the EA-treated normal rats. (3) Pre-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (8 μg) in the ACC alleviated CFA-induced affective pain (P < 0.05) and reversed the increase in firing frequency of pyramidal neurons in the ACC induced by CFA (P < 0.05). (4) Pre-treatment with the 5-HT1A receptor antagonist WAY-100635 (8 μg) in the ACC, combined with EA stimulation, reversed the CPA-like behavioral responses induced by CFA in rats and increased the firing frequency of pyramidal neurons in the ACC (P < 0.05). These results suggest that the 5-HT1A receptors in ACC mediate the alleviating effect of EA on the affective pain of CFA-induced rats.

Key words: anterior cingulate cortex (ACC); affective pain; 5-HT1A receptor; electroacupuncture (EA); in vivo multichannel electrophysiology

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通讯作者：张宇　　E-mail:

DOI: 10.13294/j.aps.2026.0008

引用本文：

申杰, 王凯妮, 高洁, 石宇, 毕涛然, 赵欣, 张宇. 前扣带皮层5-HT_1A受体介导电针缓解大鼠痛情绪[J]. 生理学报 2026; 78 (1): 233-245.

SHEN Jie, WANG Kai-Ni, GAO Jie, SHI Yu, BI Tao-Ran, ZHAO Xin, ZHANG Yu. 5-HT_1A receptors in the anterior cingulate cortex mediate electroacupuncture to alleviate the affective pain in rats. Acta Physiol Sin 2026; 78 (1): 233-245 (in Chinese with English abstract).