TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats

Ó 2014 Eur J Oral Sci

Eur J Oral Sci 2014; 122: 391–396 DOI: 10.1111/eos.12157 Printed in Singapore. All rights reserved

European Journal of Oral Sciences

TRPA1 contributes to capsaicininduced facial cold hyperalgesia in rats

Kuniya Honda1,2, Masamichi Shinoda1, Akihiko Furukawa2, Kozue Kita1, Noboru Noma3, Koichi Iwata1 1

Department of Physiology, Nihon University School of Dentistry, Tokyo; 2Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo; 3 Department of Oral Diagnosis, Nihon University School of Dentistry, Tokyo, Japan

Honda K, Shinoda M, Furukawa A, Kita K, Noma N, Iwata K. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats. Eur J Oral Sci 2014; 122: 391–396. © 2014 Eur J Oral Sci Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.

It is well known that tissue inflammation or injury of the orofacial region causes severe pain, such as burning pain or referred pain, in humans (1, 2). To examine these mechanisms, many studies have been conducted using various animal models. Orofacial administration of glutamate and lingual nerve injury induce thermal and/or mechanical hypersensitivity (3–5). Furthermore, it has been reported that facial capsaicin treatment induces both cold and heat hyperalgesia in the facial skin (6), and tissue or nerve injury induces enhancement of trigeminal ganglion (TG) neuronal excitability (7, 8). Transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thermalgated non-selective cation channels and are expressed in small- and medium-sized sensory neurons in dorsal root ganglion (DRG) and TG (9–11). Transient receptor potential vanilloid 1 can be activated by noxious heat (>43°C), extracellular acidification, and some irritants, such as capsaicin (12, 13). Transient receptor potential vanilloid 1 sensitization in ganglion neurons induces the increase of current density in response to heat stimulation and subsequent channel opening, resulting in Ca2+ influx (14, 15). Transient receptor potential vanilloid 1 is activated by cold stimulation (