Gabapentin Alleviates Neuropathic Pain and Depressive Behavior through <i>δ</i>GABA<sub>A</sub> Receptors

目的：探讨加巴喷丁对神经病理性疼痛抑郁行为的影响和机制。方法：将36只SPF级雄性C57/B6小鼠8周龄采用随机数字表法均分为3组(n = 12)：假手术组(Sham组)、神经病理性疼痛组(CCI组)和加巴喷丁组(Gap组)。采用坐骨神经慢性缩窄法(Chronic Constriction Injury, CCI)建立神经病理性疼痛模型，术后第30天Gap组腹腔注射加巴喷丁100 mg/kg，Sham和CCI组给予等容量生理盐水，连续7天。术前和术后第7、14、21、28和40 d测定各组大鼠机械缩足反应阈值(PMWT)和热缩足潜伏期(PTWL)，评价小鼠疼痛行为；术前和术后第28、40天，采用悬尾实验(TST)和高架十字迷宫实验(EPM)，评价小鼠抑郁行为。通过蛋白质免疫印迹检测小鼠海马δGABAA受体蛋白表达。结果：与Sham组相比，CCI组术后第7、14、21、28和40 d的PMWT显著下降、PTWL显著缩短(P δGABAA受体蛋白表达显著下降(P δGABAA受体蛋白表达显著增加(P δGABAA受体的表达有关。Objective: Discuss the effects and mechanisms of gabapentin on neuropathic pain and depressive behavior. Methods: 36 SPF grade male C57/B6 mice, 8 weeks old, were randomly divided into 3 groups (n = 12) using a random number table: sham group (Sham group), neuropathic pain group (CCI group), and gabapentin group (Gap group). The neuropathic pain model was established using the chronic constriction injury (CCI) of the sciatic nerve. On the 30th day post-operation, the Gap group was injected intraperitoneally with gabapentin at 100 mg/kg, while the Sham and CCI groups were given an equal volume of normal saline for 7 consecutive days. Before surgery and on day post operative 7, 14, 21, 28, and 40, the mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (PTWL) were measured in each group of rats to evaluate pain behavior; before surgery and on day post operative 28 and 40, the tail suspension test (TST) and elevated plus maze (EPM) were used to assess depressive behavior in mice. Detection of δGABAA receptor protein expression in mouse hippocampus by Western blotting. Results: Compared with the Sham group, the CCI group showed a significant decrease in PMWT and a significant shortening of PTWL on postoperative days 7, 14, 21, 28, and 40 (P δGABAA receptor protein expression was significantly decreased (P δGABAA receptor protein expression was significantly increased (P δGABAA receptors by gabapentin.