BDNF/p75NTR信号通路参与调控大鼠的神经病理性疼痛发展性进程及其炎症环境

BDNF/p75NTR Signalling Pathway is Involved in Regulating the Developmental Process of Neuropathic Pain and Its Inflammatory Milieu in Rats

目的:探讨脑源性神经营养因子(BDNF)/p75神经营养素受体(p75NTR)信号通路对大鼠神经病理性疼痛(NP)的调控作用及机制。方法:将30只大鼠中每只大鼠赋予唯一编号,并通过随机数字表生成的随机数序列分为两组(每组15只),分别命名为NP模型组(SNL组)以及其对照假手术组(Sham组)。造模完毕后,对两组大鼠进行疼痛相关行为检测,主要的行为评估包括自发性缩足次数和机械刺激及热温度刺激敏感性;采用免疫组化法以及聚合酶链反应(PCR)技术检测两组大鼠脊髓组织BDNF,p75NTR信号通路、小胶质细胞的标记蛋白离子化钙结合适配器分子1(Iba1),星形胶质细胞的标记蛋白胶质纤维酸性蛋白(GFAP)和神经元的标记蛋白神经元核抗原(NeuN)并行组间比较。结果:行为评估显示,与Sham组相比,SNL组大鼠的热痛阈值和同侧机械痛阈值显著增加;在分子水平上,与Sham组相比,SNL组大鼠的BDNF和p75NTR表达水平显著升高;SNL组大鼠小胶质细胞标记蛋白Iba1和星形胶质细胞标记蛋白GFAP的表达增加,差异均具有统计学意义(P<0.05)。神经元标记蛋白NeuN的表达在两组之间的差异无统计学意义(P>0.05)。结论:BDNF/p75NTR信号通路参与调控大鼠的病理性疼痛发展性进程及其炎症环境。BDNF和p75NTR的表达增加以及小胶质细胞和星形胶质细胞的激活,强调了以该信号通路为靶点进行潜在治疗干预的重要性。

Objective To investigate the regulation of brain-derived neurotrophic factor(BDNF)/p75 neurotrophin receptor(p75NTR)signalling pathway on neuropathic pain(NP)and its mechanism.Methods Each of the 30 rats was assigned a unique number,and a sequence of random numbers generated by the random numbers table was divided into two groups(15 rats in each group):the neuropathic pain model group(SNL)and the control sham operation group(Sham).After the modelling was completed,nociceptive behaviours of rats in each group were examined,pain-related behaviors were assessed including spontaneous paw withdrawal frequency,mechanical,and thermal sensitivity.Immunohistochemistry and polymerase chain reaction(PCR)were performed to detect BDNF,p75NTR signaling pathway,the marker protein for microglia,ionized calcium-binding adapter molecule 1(Iba1),the marker protein for astrocytes,glial fibrillary acidic protein(GFAP),and the marker protein for neurons,neuronal nuclei(NeuN),were translated and compared between groups,with parallel inter-group comparisons.Results Behavioral assessments showed significant increases in spontaneous paw withdrawal frequency and ipsilateral mechanical sensitivity in SNL rats compared to Sham rats.At the molecular level,BDNF and p75NTR expression levels were significantly elevated in SNL rats compared to Sham rats.Additionally,increased expression of microglial marker Iba1 and astrocytic marker GFAP in SNL rats.All differences were statistically significant(P<0.05).However,there was no statistically significant change in neuronal marker Neun expression between the two groups(P>0.05).Conclusion The BDNF/p75NTR signaling pathway plays a crucial role in regulating the development of neuropathic pain and its inflammatory environment in rats.The increased expression of BDNF and p75NTR,coupled with the activation of microglia and astrocytes,emphasizes the importance of targeting this signaling pathway for potential therapeutic interventions against neuropathic pain.