侧脑室内连续注射神经肽S对神经病理性疼痛大鼠疼痛及焦虑行为的影响

摘要

目的：研究侧脑室内连续注射神经肽S对神经病理性疼痛大鼠疼痛行为及焦虑行为的影响，探讨神经肽S对疼痛和焦虑影响的作用机制。方法40只雄性Sprague-Dawley大鼠被随机分为假手术对照组(Sham-Veh组)、假手术神经肽S组(Sham-NPS组)、慢性压迫性神经损伤组(CCI组)、神经肽S低剂量组(NPSl组，0.1 nmol/L)和神经肽S高剂量组(NPSh组，1 nmol/L)，每组8只。制备CCI动物模型，造模成功后第7天左侧侧脑室置入微透析用导针，自术后第8天起每日侧脑室注射相应药物，在术后第14天检测机械痛缩足阈值和热辐射缩足潜伏期，并通过高架十字迷宫检测焦虑行为的变化。采用免疫组织荧光技术检测左侧杏仁核区神经肽S受体(NPSR)的表达。结果与Sham-Veh组比较，CCI组大鼠术后14 d出现明显疼痛和焦虑行为(P<0.01)，NPSh组明显缓解(P<0.01)，NPSl组与CCI组比较无显著性差异(P>0.05)。免疫组织荧光结果显示，与CCI组相比，NPSh组杏仁核区NPSR表达明显增加。结论神经肽S可以剂量依赖性地逆转CCI大鼠的疼痛和焦虑行为，其机制可能与杏仁核NPSR上调有关。%Objective To investigate the effects of intracerebroventricular injection of neuropeptide S (NPS) on pain and anxiety behav-iors in rats with neuropathic pain, and explore the possible mechanism. Methods 40 male Sprague-Dawley rats were randomly divided into Sham-Vehicle group, Sham-NPS group, chronic constriction injury (CCI) group, Neuropeptide S low-dose group (NPSl group, 0.1 nmol/L) and Neuropeptide S high-dose group (NPSh group, 1 nmol/L), with 8 rats in each group. Pain-related behaviors, anxiety-related behaviours, and expression of NPS receptor (NPSR) in the left amygdaloid nucleus were measured on the 14th day via intracerebroventricular injection. Results Compared with the Sham-Vehicle group, the CCI group demonstrated significant pain and anxiety behaviors 14 days after operation (P<0.01), the NPSh group significantly relieved (P<0.01). And there was no significant difference between the NPSl group and the CCI group (P>0.05). Compared with the CCI group, NPSR expression in amygdaloid nucleus increased in the NPSh group. Conclusion NPS can dose-dependently relieve the pain and anxiety behaviors in CCI rats, which may be related with the increase of NPSR in amygdaloid nucleus.