骨癌痛大鼠脊髓背角KCC2的表达及可能机制

目的研究骨癌痛大鼠脊髓背角钾离子-氯离子联合转运体2(potassium-chloride cotransporter2,KCC2)的表达变化及其可能机制。方法采用大鼠胫骨骨髓腔接种Walker256肿瘤细胞建立胫骨癌痛模型。观测种瘤前后大鼠机械缩足反射阈值(mechanical withdrawl thresthold,MWT)和脊髓背角KCC2表达水平的变化,观察痛敏形成前鞘内预注射酪氨酸蛋白激酶B(tyrosine protein kinase B,TrkB)中和抗体阻断脑源性神经营养因子(brain-derived neurotrophic factor,BD-NF)-TrkB途径对KCC2表达和机械性痛觉超敏的影响。结果大鼠种瘤后6～12d,MWT明显下降(P<0.01),出现明显的机械性痛敏,脊髓背角KCC2蛋白水平进行性降低(P<0.01);鞘内预注射TrkB中和抗体的骨癌痛大鼠,其脊髓KCC2表达水平和MWT明显高于注射IgG和不作处理的骨癌痛大鼠(P<0.01)。结论脊髓背角的KCC2可能参与了骨癌痛的发生发展,而BDNF-TrkB途径可能介导了该作用。

Mechanism and expression of KCC2 in the spinal cord of bone cancer pain rats

Aim To research expression change of potassium-chloride cotransporter 2,(KCC2) in the dorsal horn of spinal cord in bone cancer pain rats and its possible mechanism.Methods The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity.The change of the mechanical withdrawl thresthold(MWT) and the expression level of KCC2 in spinal dorsal horn in rats at pre-and post-inoculation were observed,and the effect of blocked endogenous brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) pathway by intrathecal pretreatment with TrkB Ab on KCC2 expression and mechanical allodynia was observed.Results From the 6th to 12th day post-inoculation,MWT was significantly decreased(P<0.01),and appeared visible mechanical allodynia,Spinal KCC2 protein levels were progressively reduced(P<0.01),KCC2 protein levels in the dorsal horn of spinal cord and MWT from TrkB Ab pretreated bone cancer pain rats were highly relative to that of IgG-and none-treated rats(P<0.01).Conclusions These results indicate that KCC2 in dorsal horn of Spinal cord may be involved in the development of bone cancer pain,and KCC2 downregulation probably mediated by BDNF-TrkB pathway.