Temporomandibular Joint Inflammation Potentiates the Excitability of Trigeminal Root Ganglion Neurons Innervating the Facial Skin in Rats

Abstract

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.

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

“…Initially, we used a retrograde tracer to identify neurons that provide sensory innervation to the TMJ capsule within the posterior lateral region of the trigeminal ganglion. Neuronal cell bodies were arranged in discrete bands within the mandibular region of the ganglion as reported in a previous study (Takeda et al, 2005). We found that the majority of the neurons providing innervation of the TMJ capsule co-expressed CGRP and the TRPV1 receptor.…”

Satellite glial cells in sensory ganglia: its role in pain

“…31,43 This was later confirmed after finding that the increased release of substance P by A␦ and C nociceptors was accompanied by an increased expression of NK1 receptors in A␤ non-nociceptive surrounding neurons. 44,45 Moreover, it has been suggested that this neuropeptide can activate the SGC through NK1 receptors, so that SGC respond with the synthesis and release of IL1-␤. 22 The NK1 expression in SGC was not directly measured, but the NK1expression with high affinity for substance P has been shown in astrocytes and microglia.…”

Anatomical changes within the medullary dorsal horn in chronic temporomandibular disorder pain

“…Animal models of temporomandibular joint inflammation reveal upregulation of glial cells, increased neuron-glia communication, and enhanced neuronal excitability within the trigeminal ganglion (Takeda et al, 2005;Villa et al, 2010). Whilst our findings of increased MD (loss of barriers limiting water movement) coupled with decreased FA (loss of directional coherence/altered structural organisation) in the trigeminal nerve are usually interpreted as markers of neuronal degeneration, they may also reflect chronic inflammation (Assaf and Pasternak, 2008;Tievsky et al, 1999).…”