【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。更多还原

【Abstract】 【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 Nav1.3 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 min before L5-VRT,all of these significantly inhibited the expression of Nav1.3 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 L5-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.更多还原