脊柱小胶质细胞中src家族激酶的活化通过p38通路参与甲醛诱导性持续疼痛状态

Fu, K.-Y.; Center for TMD and Orofacial Pain, Peking University, School and Hospital of Stomatology, Zhong Guan Cun South Avenue 22, Beijing 100081, China; email:kqkyfu@bjmu.edu.cn

Protein tyrosine phosphorylation has been implicated in normal and pathological functions such as cell proliferation, migration and differentiation. Recently, some studies have shown that Src family kinases (SFKs) were involved in neurological disorders and neuropathic pain states in which microglial activation plays a role. In the formalin test, we have reported that microglia undergo at least 2 distinct stages of activation on the basis of signaling events regarding p38 mitogen-activated protein kinases (MAPK). Here, we investigated the involvement of SFKs signaling in a formalin pain animal model and the association with p38 MAPK. Our results showed that SFKs were activated in the spinal microglia beginning 1 day after peripheral formalin injection lasting for 7 days. Pretreatment with SFK specific inhibitor PP2 could not inhibit formalin-induced spontaneous pain behaviors. However, PP2 inhibited formalin injury, induced persistent mechanical hyperalgesia, and reversed microglial phospho-p38 expression as well using immunohistostaining and Western blot at day 3 and 7 after injection. Our results suggested that the activation of the Src/p38MAPK signaling cascade in spinal microglia contributed to late stage persistent mechanical hyperalgesia evoked by formalin injection into the paw. Perspective: This study presents unique properties of spinal microglial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal microglia to acute and persistent pain state. © 2012 by the American Pain Society.

Center for TMD and Orofacial Pain, Peking University, School and Hospital of Stomatology, Zhong Guan Cun South Avenue 22, Beijing 100081, China