Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain

Abstract: 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_V1.7 and the tetrodotoxin-resistant (TTX-R) Na_V1.8 and Na_V1.9 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_V1.7 and Na_V1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. In the present study, the expression of Na_V1.7, Na_V1.8 and Na_V1.9 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_V1.7, Na_V1.8 and Na_V1.9 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_V1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na_V1.7 and Na_V1.8 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_V1.7, Na_V1.8 and Na_V1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult. [Copyright &y& Elsevier]