Temporomandibular joint inflammation potentiates the excitability of trigeminal root ganglion neurons innervating the facial skin in rats.

The aim of this study was to test the hypothesis that temporomandibular joint (TMJ) inflammation alters the excitability of trigeminal root ganglion (TRG) neurons innervating the facial skin, by using behavioral, electrophysiological, molecular, and immunohistochemical approaches. Complete Freund's adjuvant (CFA) was injected into the rat TMJ to produce inflammation. The threshold for escape from mechanical stimulation applied to the orofacial area in TMJ-inflamed rats was significantly lower than that in naïve rats. The TRG neurons innervating the inflamed TMJ were labeled by 2% Fluorogold (FG) injection into the TMJ. The number of FG-labeled substance P (SP)-immunoreactive neurons in the inflamed rats was significantly increased compared with that in the naïve rats. On the other hand, medium- and large-diameter TRG neurons (>30 microm) innervating the facial skin were labeled by FG injection into the facial skin. In the FG-labeled cutaneous TRG neurons, the occurrence of SP (100 nM) induced membrane depolarization in inflamed rats (medium: 73.3%, large : 85.7%) was larger than that in the naïve rats (medium: 29.4%, large : 0%). In addition, SP application significantly increased the firing rate evoked by depolarizing pulses in the neurons of inflamed rats compared with those of naïve rats. Quantitative single-cell RT-PCR analysis showed the increased expression of mRNA for the NK1 receptor in FG-labeled TRG neurons in inflamed rats compared with that in naive rats. The numbers of SP and NK1 receptors/neurofilament 200 positive immunoreactive TRG neurons innervating the facial skin (FG-labeled) in the inflamed rats were significantly increased compared with those seen in naïve rats. These results suggest that TMJ inflammation can alter the excitability of medium- and large-diameter TRG neurons innervating the facial skin and that an increase in SP/NK1 receptors in their soma may contribute to the mechanism underlying the trigeminal inflammatory allodynia in the TMJ disorder.