CUTANEOUS INFLAMMATION REGULATES THIK1 EXPRESSION IN DORSAL ROOT GANGLION NEURONS

JUAN MERCADO; CRISTIAN ACOSTA; SERGIO BENITEZ

Mendoza

Encuentro; XXXIV REUNIÓN CIENTIFICA ANUAL DE LA SOCIEDAD DE BIOLOGÍA DE CUYO; 2016

Sociedad de Biología de Cuyo

THIK1is a two-pore-domain potassium channel present in a variety of tissuesincluding arterial endothelium, kidney and in neurons of the retrotrapezoidnucleus and the trigeminal ganglia. We previously demonstrated that THIK1 mRNAis present in dorsal root ganglia (DRG) and that its levels droppedipsilaterally 1 day after CFA-induced cutaneous inflammation (CFA1). However,the identity of the DRG subpopulations expressing THIK1 and the specifics ofany relationship to inflammatory pain, remain unknown. Using a combination ofimmunohistochemistry, western blotting and behaviour in normal and CFA-treatedrats we elucidated the cellular localization and inferred physiologicalproperties of THIK1. In normal rats, we found that all small neurons andsubpopulations of medium and large DRG neurons express THIK1. THIK1 staining isweakly positively correlated with IB4-binding but strongly positivelycorrelated with trkA suggesting that THIK1 is expressed by nociceptors. AtCFA1, cytoplasmic THIK1 staining was significantly reduced only in smallneurons ipsilaterally compared to normal. At 4 days after inflammation (CFA4),THIK1 staining increased significantly ipsilaterally in medium and largeneurons compared to normal. THIK1 levels in small neurons increasedipsilaterally compared to contralateral but did not differ significantly fromnormal. Finally, ipsilateral (but not contralateral) mean %intensities of THIK1in small neurons at CFA1 correlated strongly negatively with spontaneous footlifting duration (a marker of spontaneous pain). Our results demonstrate THIK1expression in DRG neuron subpopulations that are likely to include nociceptors.Interestingly, THIK1 is regulated by cutaneous inflammation and it might be implicated in the pathogenesis of spontaneous pain.