Zhou X-L, Zhang C-J, Wang Y, Wang M, Sun L-H, Yu L-N, Cao J-L, Yan M
Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
Neuroscience. 2015 Oct 29;307:64-72. doi: 10.1016/j.neuroscience.2015.08.048. Epub 2015 Aug 28.
Spinal ephrinB-EphB signaling is involved in the modulation of pain processing. The aim of the present study was to investigate whether protein kinase C-γ (PKCγ) acts as a downstream effector in regulating spinal pain processing associated with ephrinB-EphB signaling in mice. The intrathecal injection of ephrinB2-Fc, an EphB receptor activator, caused thermal hyperalgesia and mechanical allodynia, as well as increased activation of spinal PKCγ. Knockdown of spinal PKCγ prevented the pain behaviors induced by ephrinB2-Fc. Furthermore, the intrathecal injection of EphB2-Fc, an EphB receptor blocker, suppressed formalin-induced inflammatory, chronic constriction injury (CCI)-induced neuropathic, and tibia bone cavity tumor cell implantation (TCI)-induced bone cancer pain behaviors, in addition to reducing the activation of spinal PKCγ. Finally, the intrathecal injection of MK801, an N-methyl-D-aspartate (NMDA) receptor blocker, prevented the pain behaviors and spinal PKCγ activation induced by ephrinB2-Fc. Overall, the results confirm the important role of PKCγ in the regulation of spinal pain processing associated with ephrinB-EphB signaling.
脊髓ephrinB-EphB信号通路参与疼痛处理的调节。本研究的目的是调查蛋白激酶C-γ（PKCγ）是否作为一种下游效应分子，在调节小鼠中与ephrinB-EphB信号通路相关的脊髓疼痛处理过程中发挥作用。鞘内注射EphB受体激活剂ephrinB2-Fc会导致热痛觉过敏和机械性异常疼痛，同时脊髓PKCγ的激活也会增加。脊髓PKCγ的敲低可预防ephrinB2-Fc诱导的疼痛行为。此外，鞘内注射EphB受体阻断剂EphB2-Fc，除了可降低脊髓PKCγ的激活外，还可抑制福尔马林诱导的炎症性疼痛、慢性压迫性损伤（CCI）诱导的神经性疼痛以及胫骨骨腔肿瘤细胞植入（TCI）诱导的骨癌疼痛行为。最后，鞘内注射N-甲基-D-天冬氨酸（NMDA）受体阻断剂MK801可预防ephrinB2-Fc诱导的疼痛行为和脊髓PKCγ激活。总体而言，这些结果证实了PKCγ在调节与ephrinB-EphB信号通路相关的脊髓疼痛处理过程中的重要作用。
