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Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway.
J Pain. 2012 Oct; 13(10):1008-15.JP

Abstract

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.

Authors+Show Affiliations

Center for TMD & Orofacial Pain, Peking University School & Hospital of Stomatology, Beijing, P R China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23031400

Citation

Tan, Yong-Hui, et al. "Activation of Src Family Kinases in Spinal Microglia Contributes to Formalin-induced Persistent Pain State Through P38 Pathway." The Journal of Pain : Official Journal of the American Pain Society, vol. 13, no. 10, 2012, pp. 1008-15.
Tan YH, Li K, Chen XY, et al. Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway. J Pain. 2012;13(10):1008-15.
Tan, Y. H., Li, K., Chen, X. Y., Cao, Y., Light, A. R., & Fu, K. Y. (2012). Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway. The Journal of Pain : Official Journal of the American Pain Society, 13(10), 1008-15. https://doi.org/10.1016/j.jpain.2012.07.010
Tan YH, et al. Activation of Src Family Kinases in Spinal Microglia Contributes to Formalin-induced Persistent Pain State Through P38 Pathway. J Pain. 2012;13(10):1008-15. PubMed PMID: 23031400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway. AU - Tan,Yong-Hui, AU - Li,Kai, AU - Chen,Xin-Yi, AU - Cao,Ye, AU - Light,Alan R, AU - Fu,Kai-Yuan, PY - 2012/03/30/received PY - 2012/05/31/revised PY - 2012/07/21/accepted PY - 2012/10/4/entrez PY - 2012/10/4/pubmed PY - 2013/3/15/medline SP - 1008 EP - 15 JF - The journal of pain : official journal of the American Pain Society JO - J Pain VL - 13 IS - 10 N2 - UNLABELLED: 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. SN - 1528-8447 UR - https://www.unboundmedicine.com/medline/citation/23031400/Activation_of_Src_family_kinases_in_spinal_microglia_contributes_to_formalin_induced_persistent_pain_state_through_p38_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-5900(12)00743-2 DB - PRIME DP - Unbound Medicine ER -