Yin Xuan, Zeng Xiao-Ling, Lin Jing-Jing, Xu Wen-Qing, Cui Kai-Yu, Guo Xiu-Tian, Li Wei, Xu Shi-Fen
Department of Acupuncture and Moxibustion, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Department of Anorectal Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
J Integr Med. 2025 Mar;23(2):159-168. doi: 10.1016/j.joim.2025.01.006. Epub 2025 Jan 27.
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
疼痛与抑郁共病情况常见，但治疗仍具难度。电针（EA）可有效改善抑郁症状并缓解疼痛，但其神经机制尚不明晰。因此，我们通过眶下神经缩窄（CION）建立小鼠疼痛模型，随后对这些动物进行电针治疗，并利用静息态功能磁共振成像（rs-fMRI）检测脑部变化。
40只雄性C57BL/6J小鼠分为4组：对照组、CION模型组、电针组和假针刺组（不进针）。于百会（GV20）和足三里（ST36）穴位进行电针治疗20分钟，每日1次，连续10天。术后3天及干预后每3天测试机械缩足阈值。采用悬尾试验、旷场试验、高架十字迷宫（EPM）、蔗糖偏好试验和埋大理石试验评估抑郁行为。利用rs-fMRI检测电针治疗后小鼠功能连接（FC）的脑部变化。
与CION组相比，干预结束时电针组机械缩足阈值升高（P < 0.05）；悬尾试验中不动时间缩短（P < 0.05）；EPM中进入开放臂次数及在开放臂停留时间增加（均P < 0.001）。蔗糖偏好试验和埋大理石试验无差异（均P > 0.05）。功能磁共振成像结果显示，电针治疗使低频波动幅度和局部一致性值下调，而在疼痛与抑郁共病的CION模型中，杏仁核、海马体和大脑皮层等脑区这些指标升高。以杏仁核为种子区，我们发现CION组的FC高于对照组。同时，电针治疗能够降低杏仁核与包括尾壳核、丘脑及部分大脑皮层在内的其他脑区之间的FC。
电针可下调杏仁核神经元的异常激活，并改善其与其他脑区之间的FC，从而发挥镇痛和抗抑郁作用。请引用本文：Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 202(25); 23(2): 159-168.
