Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury.

Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Research Abstract Details 

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Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Abstract Text:

Makoto Tsuda,Hidetoshi Tozaki-Saitoh,Takahiro Masuda,Emika Toyomitsu,Tohru Tezuka,Tadashi Yamamoto,Kazuhide Inoue,Makoto Tsuda,Hidetoshi Tozaki-Saitoh,Takahiro Masuda,Emika Toyomitsu,Tohru Tezuka,Tadashi Yamamoto,Kazuhide Inoue,Makoto Tsuda,Hidetoshi Tozaki-Saitoh,Takahiro Masuda,Emika Toyomitsu,Tohru Tezuka,Tadashi Yamamoto,Kazuhide Inoue,Makoto Tsuda,Hidetoshi Tozaki-Saitoh,Takahiro Masuda,Emika Toyomitsu,Tohru Tezuka,Tadashi Yamamoto,Kazuhide Inoue,

Neuropathic pain, a debilitating chronic pain following nerve damage, is a reflection of the aberrant functioning of a pathologically altered nervous system. One hallmark is abnormal pain hypersensitivity to innocuous stimuli (tactile allodynia), for which effective therapy is lacking, and the underlying mechanisms of which remain to be determined. Here we show that Lyn, a member of the Src family kinases (SFKs), plays an important role in the pathogenesis of neuropathic pain. Nerve injury, but not peripheral inflammation, increased immunoreactivity for active SFKs that were autophosphorylated in the kinase domain (phospho-SFK-IR) in spinal microglia. In spinally derived microglial cells, we identified Lyn as the predominant SFK among the five members (Src, Fyn, Yes, Lck, and Lyn) known to be expressed in the CNS. Lyn expression in the spinal cord was highly restricted to microglia, and its level was increased after nerve injury. We found that mice lacking lyn (lyn(-/-)) exhibit a striking reduction in the levels of phospho-SFK-IR and tactile allodynia after nerve injury, without any change in basal mechanical sensitivity or inflammatory pain. Importantly, lyn(-/-) mice displayed impaired upregulation of the ionotropic ATP receptor subtype P2X(4) receptors (P2X(4)R) in the spinal cord after nerve injury, which is crucial for tactile allodynia. Microglial cells from lyn(-/-) mice showed a deficit in their ability to increase P2X(4)R expression in response to fibronectin, a factor implicated as a microglial P2X(4)R upregulator in allodynia. Together, our findings suggest that Lyn may be a critical kinase mediating nerve injury-induced P2X(4)R upregulation and neuropathic pain. (c) 2007 Wiley-Liss, Inc.

Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Publishing Authors By Initials

M Tsuda,H Tozaki-Saitoh,T Masuda,E Toyomitsu,T Tezuka,T Yamamoto,K Inoue,M Tsuda,H Tozaki-Saitoh,T Masuda,E Toyomitsu,T Tezuka,T Yamamoto,K Inoue,M Tsuda,H Tozaki-Saitoh,T Masuda,E Toyomitsu,T Tezuka,T Yamamoto,K Inoue,M Tsuda,H Tozaki-Saitoh,T Masuda,E Toyomitsu,T Tezuka,T Yamamoto,K Inoue,

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Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Glia

VOLUME: 56

Page Numbers: 50-8

Journal Abbreviation: Glia

ISSN: 0894-1491

DAY: 1

MONTH: Jan

YEAR: 2008

Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Information

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LANGUAGE: eng

NlmUniqueID: 8806785

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AFFILIATION: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi, Fukuoka, Japan.

Country: United States

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MEDLINETA: Glia

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