NF-KappaB、p38 MAPK和JNK通路在运动神经损伤引起的大鼠病理性疼痛中的作用及机制  

Role of NF-KappaB,p38 MAPK,and c-jun N-terminal Kinase in Neuropathic Pain Rats Following Motor Nerve Injury

作　　者：臧颖[1] 陈秋英[1] 李玉莹[1] 刘先国[1] 

机构地区：[1]中山大学疼痛研究中心中山医学院生理教研室,广东广州510080

出　　处：《中山大学学报（医学科学版）》2009年第6期645-651,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金青年基金(30900436)

摘　　要：【目的】探讨肿瘤坏死因子α(TNF-α)激活的下游信号转导途径-核转录因子kappaB(NF-κB)、JNK和p38MAPK是否参与运动神经损伤引起的大鼠病理性疼痛的形成,并探讨其可能机制。【方法】采用痛行为学测试和免疫荧光组织化学方法,观察蛛网膜下腔内注射NF-κB抑制剂(PDTC)、p38 MAPK抑制剂(SB203580)和JNK抑制剂(SP600125)对腰5脊神经前根切断(L5-VRT)大鼠机械性痛过敏及腰5背根神经节(DRG)内电压门控钠通道(Nav1.3)表达的影响。【结果】①L5-VRT术前应用NF-κB抑制剂PDTC可完全抑制大鼠双侧机械性痛过敏的形成,并阻断同侧L5 DRG内Nav1.3的上调;②术前应用p38 MAPK抑制剂SB203580和JNK抑制剂SP600125主要抑制大鼠对侧后肢的机械性痛过敏;对手术同侧DRG内Nav1.3的表达,SB203580和SP600125分别具有完全阻断和部分阻断作用;③术后7 d给予PDTC或SB203580或SP600125对已形成的大鼠机械性痛过敏均无影响。【结论】运动神经损伤可能通过NF-κB、p38 MAPK和JNK途径调控未损伤DRG神经元内Nav1.3的表达从而进一步调控L5-VRT引起的大鼠后肢机械性痛过敏。[Objective] To test the idea that the downstream molecules of TNF-α [NF-kappa B, p38 MAPK, and c-jun N- terminal kinase （JNK） ] might be involved in the development of neuropathic pain induced by L5 ventral root transection （L5- VRT）. [Method] The behavioral test and the method of immunofluorescence staining were used to observe the affections of the three inhibitors of NF-kappa B, p38 MAPK, and JNK on the mechanical allodynia induced by L5 VRT and the expression of Navl.3 in L5 dorsal root ganglion （DRG）. [Result] Intrathecal injection of NF-kappa B inhibitor （PDTC） or JNK inhibitor （SP600125） or p38 inhibitor （SB203580）, administered 10 rain before L5-VRT, all of these significantly inhibited the expression of Navl.3 in ipsilateral L5 DRGs. Single pre-treatment of PDTC completely attenuated bilateral mechanical allodynia. Intrathecal injection of SB203580 or SP600125 being applied 10 min before LS-VRT and once daily thereafter until day 7 after surgery, attenuated the contralateral, but not the ipsilateral, mechanical allodynia. [Conclusion] NF-κB, p38 MAPK, and JNK pathways, through down-regulating the expression of Nav1.3 in L5 DRG, could inhibit the rat mechanical allodynia induced by motor nerve injury.

关 键 词：痛超敏 肿瘤坏死因子-αNF—kappaB p38 MAPK JNK 钠通道 

分 类 号：R338.7[医药卫生—人体生理学]