脊髓背角SGK-1调控NF-κB信号通路参与强直刺激坐骨神经引起的慢性疼痛

The role of SGK-1 in the spinal cord in tetanic sciatic stimulation-induced chronic pain by activating NF-κB

目的研究脊髓背角血清和糖皮质激素调节激酶1(SGK-1)在强直刺激坐骨神经(HFS)引起的慢性疼痛中的作用,并初步探讨其作用机制。方法将48只SD大鼠随机分为4组:control组、HFS组、生理盐水+HFS组、SGK-1抑制剂(GSK 650394)+HFS组,行50%机械刺激撤足阈值测定、在体电生理方法记录脊髓背角C纤维诱发电位的幅度和免疫组化染色检测脊髓背角SGK-1及NF-κB p65磷酸化情况。结果强直刺激坐骨神经引起脊髓背角C纤维诱发电位长时程增强(LTP)以及触诱发痛(P<0.01);强直刺激坐骨神经导致脊髓背角神经元p-SGK-1表达上调(P<0.01);鞘内给予SGK-1抑制剂GSK650394阻断强直刺激坐骨神经引起的脊髓背角LTP以及抑制触诱发痛;SGK-1抑制剂抑制了强直刺激坐骨神经引起的脊髓背角NF-κB信号通路的激活(P<0.01)。结论SGK-1可能在强直刺激坐骨神经后过表达,并且通过激活NF-κB信号通路促进慢性疼痛的发展。

Objective To investigate the role of SGK-1 in the spinal cord in chronic pain induced by tetanic stimulation of sciatic nerve and the related mechanisms.Methods All 48 SD rats were randomly divided into 4 groups:control group,HFS group,saline+HFS group and GSK 650394+HFS group.The amplitude of C-fiber evoked potential in spinal dorsal horn was detected by in vivo electrophysiological.The expressions of p-SGK-1 and p-p65 in spinal dorsal horn were detected by Immunohistochemistry.Results High frequency stimulation of the sciatic nerve(HFS)induced long-term potentiation and chronic pain hypersensitivity(P<0.01).HFS resulted in the upregulation of p-SGK-1 in the spinal dorsal horn(P<0.01).SGK-1 inhibitor GSK-650394 prevented the induction of long term potentiation,the development of pain hypersensitivity;GSK-650394 also inhibited the expression of p-p65 in the spinal dorsal horn following HFS(P<0.01).Conclusion The phosphorylation of SGK-1 in the spinal dorsal horn was overexpressed after HFS,and contributed the development of pain hypersensitivity after HFS by activating p-p65.