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Changes in the expression of Na V 1.7, Na V 1.8 and Na V 1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain
Author(s) -
Strickland Iain T.,
Martindale Jo C.,
Woodhams Peter L.,
Reeve Alison J.,
Chessell Iain P.,
McQueen Daniel S.
Publication year - 2008
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2007.09.001
Subject(s) - sodium channel , population , dorsal root ganglion , chemistry , tetrodotoxin , downregulation and upregulation , medicine , immunohistochemistry , sodium , microbiology and biotechnology , endocrinology , anatomy , dorsum , biology , biochemistry , gene , environmental health , organic chemistry
Voltage‐gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin‐sensitive (TTX‐S) Na V 1.7 and the tetrodotoxin‐resistant (TTX‐R) Na V 1.8 and Na V 1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na V 1.7 and Na V 1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post‐insult. In the present study, the expression of Na V 1.7, Na V 1.8 and Na V 1.9 was examined over a 28 day timecourse during a rat model of FCA‐induced chronic inflammatory joint pain. Using the retrograde tracer Fast Blue (FB) and specific Na V 1.7, Na V 1.8 and Na V 1.9 sodium channel antibodies, immunohistochemical staining techniques were used to study sodium channel expression in a distinct population of L3–L5 knee joint afferent DRGs. In the ganglia, counts were made of positively labelled cells in the FB population. The results demonstrate that, following FCA injection, Na V 1.9 expression is upregulated at days 14, 21 and 28 post‐FCA, with Na V 1.7 and Na V 1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA‐injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na V 1.7, Na V 1.8 and Na V 1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult.