Involvement of transient receptor potential vanilloid 1 channel expression in orofacial cutaneous hypersensitivity following tooth pulp inflammation

Abstract

A study was conducted to evaluate the mechanisms underlying ectopic orofacial pain associated with tooth pulp inflammation in rats. We observed a significant decrease in the head withdrawal threshold (HWT) response to mechanical and heat stimuli applied to the ipsilateral facial skin upon application of complete Freund's adjuvant (CFA) to the upper first molar (M1TP) in comparison to application of vehicle. A large number of trigeminal ganglion (TG) neurons showed transient receptor potential vanilloid 1 (TRPV1) immunoreactivity (IR), and some of them were retrogradely labeled with fluorogold injected into the facial skin. A large number of cells showing IR for glial fibrillary acidic protein (GFAP) were observed in the 2nd compared to the 1st or 3rd branch regions of the TG, and TG cells innervating the facial skin were also surrounded by GFAP-IR cells. After administration of TRPV1 antagonist into the facial skin of M1TP CFA-treated rats, the decrease of HWTs in response to mechanical and heat stimulation of the facial skin was significantly reversed. The present findings suggest that the excitability of TG neurons is enhanced upon tooth pulp inflammation, leading to overexpression of TRPV1 in TG neurons innervating the facial skin, and that satellite glial cells are also activated, resulting in the development of ectopic orofacial pain.

Role of transient receptor potential vanilloid type 1 in the trigeminal ganglion and brain stem following dental pulp inflammation

“…Previous studies have demonstrated that TRPV1 expression in TG is modulated by a wide range of stimulus intensities, from minor tooth injury (Chung et al 2011) to severe pulp inflammation (Tarsa et al 2010, Matsuura et al 2013. Therefore, the significantly higher density of TRPV1-positive cells observed in the CFA group was not a surprising finding and was in line with previous reports (Watase et al 2018). However, a notable outcome in the present study was the predominant expression of TRPV1 in small-sized TG neurons, as an important contributor to orofacial nociception (Kanazawa & Matsumoto 2014).…”

“…Therefore, the significantly higher density of TRPV1‐positive cells observed in the CFA group was not a surprising finding and was in line with previous reports (Watase et al . ). However, a notable outcome in the present study was the predominant expression of TRPV1 in small‐sized TG neurons, as an important contributor to orofacial nociception (Kanazawa & Matsumoto ).…”

“…Recently, CFA has been frequently used to study pulpal pain (Matsuura et al 2013, Filippini et al 2018, Watase et al 2018. Further, a rapid onset of definitive pain was observed.…”

“…, Watase et al . ). Evidence for the involvement of TRPV1 channels in orofacial pain mechanisms has recently been reinforced by reports on the efficacy of TRPV1 antagonists in preclinical models of inflammatory pulp pain (Araya et al .…”

“…Although the mechanisms underlying intense pulpal pain are not fully understood, research has focused on the molecular responses to inflammation in the peripheral and central nervous systems (PNS and CNS, respectively;Chiang et al 1998, Fehrenbacher et al 2009, Matsuura et al 2013. When inflammation occurs in orofacial tissues, such as the dental pulp, a substantial up-regulation of transient receptor potential vanilloid type 1 (TRPV1) expression is observed in afferent trigeminal ganglion (TG) neurons, leading to modulation of C-fibre afferent excitability (Matsuura et al 2013, Watase et al 2018. Evidence for the involvement of TRPV1 channels in orofacial pain mechanisms has recently been reinforced by reports on the efficacy of TRPV1 antagonists in preclinical models of inflammatory pulp pain (Araya et al 2017).…”