前扣带回内肿瘤坏死因子α过表达在神经病理性疼痛中的作用

Role of TNF-α in Anterior Cingulate Cortex in Neuropathic Pain Induced by Sciatic Nerve Injury

【目的】探讨坐骨神经部分损伤对前扣带回(ACC)内致炎细胞因子TNF-α、IL-1β和抗炎细胞因子IL-10表达的影响,并分析它们在神经病理性疼痛中的可能作用。【方法】采用行为学、Western blot、免疫荧光组织化学方法,观察外周神经损伤后ACC内上述细胞因子表达的改变以及ACC内微量注射相应中和抗体对大鼠痛行为的影响。【结果】(1)坐骨神经部分损伤(SNI)诱导大鼠损伤侧触诱发痛并伴有ACC内致炎细胞因子TNF-α和抗炎细胞因子IL-10蛋白水平显著升高,其中TNF-α升高幅度更大,但对IL-1β的表达无影响;(2)免疫荧光双染结果表明SNI后ACC内上调的TNF-α以及IL-10都表达于神经元而非胶质细胞内;(3)通过SNI术前及术后连续多次在ACC内微量注射TNF-α中和抗体,显著缓解大鼠触诱发痛,但给予IL-1β中和抗体对大鼠痛行为无影响。【结论】以上结果表明坐骨神经损伤可能通过诱导ACC神经元内TNF-α异常分泌易化脊髓背角痛信息传入。

【Objective】To discuss the effect of sciatic nerve injury on the expressions of tumor necrosis factor-alpha（TNF-α）,interleukin-1β（IL-1β）and interleukin-10（IL-10）in anterior cingulate cortex（ACC）,and further to explain their roles resided in the development of neuropathic pain.【Method】With use of the methods of behavioral test,western blot and immunohistochemistry,we examine the effects of spared sciatic nerve injury（SNI）on the expressions of TNF-α,IL-1β,and IL-10 in ACC,and observe the effect of the neutralizing antibody of TNF- α,IL-1β on the rat mechanical allodynia.【Result】In present experiment,SNI increased the protein levels of TNF-α,IL-10,but not IL-1β in ACC. Increased TNF-α-IR and IL-10-IR in ACC is located in neurons,but not astrocytes and microglia at 7 d following L5-VRT. Pre-treatment with anti-TNFα antibody but not anti-IL-1βantibody into ACC significantly increased the rat paw withdrawal threshold to von Frey hairs.【Conclusion】These data suggested that the increased TNF-α in ACC neurons might be responsible for the development of neuropathic pain.