早期脊髓电刺激对大鼠脊髓损伤后疼痛的镇痛机制研究

Analgesic mechanism study of neuropathic pain relieved by early spinal cord stimulation in rats with spinal cord injury

摘要:

目的：探究脊髓电刺激对脊髓损伤大鼠神经病理性疼痛的疗效和脊髓背角内瞬时受体电位通道香草醛亚型1（transient receptor potential vanilloid 1, TRPV1）和C-C趋化因子配体2（C-C chemokine ligand 2, CCL2）表达的影响。方法：雌性SD大鼠64只按随机数字表法分成4组：空白对照组、假手术组、脊髓损伤组、脊髓损伤+电刺激组，每组16只。观察术前、术后7天和术后14天机械刺激缩足阈（paw mechanical withdrawal threshold, PMWT）和热痛缩足阈（thermal withdrawal latency, TWL）的变化，采用qPCR法和Western Blot法分别检测TRPV1和CCL2 mRNA和蛋白表达，ELISA法检测炎性细胞因子IL-6、IL-1β和TNFα含量。结果：与空白对照和假手术组比较，术后7、14天脊髓损伤组大鼠50% PMWT和TWL降低、TRPV1和CCL2转录和表达增强（P <0.05）、IL-6、IL-1β和TNFα表达增加（P <0.001）；与脊髓损伤组比较，脊髓损伤+电刺激组50% PMWT和 TWL均上升、TRPV1和CCL2转录和表达减弱（P <0.05）、IL-6、IL-1β和TNFα表达降低（P <0.05）。结论：脊髓电刺激可能通过抑制TRPV1和CCL2表达、减轻炎症反应，缓解脊髓损伤后神经病理性疼痛。

Abstract:

Objective: To investigate the efficacy of spinal cord electrical stimulation on neuropathic pain in rats with spinal cord injury and its effects on the expression of transient receptor potential vanilloid 1 (TRPV1) and C-C chemokine ligand 2 (CCL2) in the spinal cord dorsal horn. Methods: Sixty-four female SD rats were randomly divided into four groups: control group, sham surgery group, spinal cord injury group, and spinal cord injury + electrical stimulation group, with 16 rats in each group. Changes in paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) were observed before surgery, 7 days post-surgery, and 14 days post-surgery. TRPV1 and CCL2 mRNA and protein expression were detected using qPCR and Western Blot, respectively, and the levels of inflammatory cytokines IL-6, IL-1β, and TNFα were measured by ELISA. Results: Compared to the blank control and sham surgery groups, rats in the spinal cord injury group showed a decrease in 50% PMWT and TWL, enhanced transcription and expression of TRPV1 and CCL2 (P < 0.05), and increased expression of IL-6, IL-1β, and TNFα (P < 0.001) at 7 and 14 days post-surgery. In comparison to the spinal cord injury group, the spinal cord injury + electrical stimulation group exhibited an increase in 50% PMWT and TWL, a reduction in transcription and expression of TRPV1 and CCL2 (P < 0.05), and a decrease in the expression of IL-6, IL-1β, and TNFα (P < 0.05). Conclusion: Spinal cord electrical stimulation may alleviate neuropathic pain after spinal cord injury by inhibiting the expression of TRPV1 and CCL2 and mitigating the inflammatory response.