Activation of Src Family Kinases in Spinal Microglia Contributes to Formalin-Induced Persistent Pain State Through p38 Pathway

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 micro glial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal micro glia to acute and persistent pain state. (C) 2012 by the American Pain Society. Published by Elsevier Inc. All rights reservedhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000310042600012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Clinical NeurologyNeurosciencesSCI(E)PubMed10ARTICLE101008-10151