The pathophysiological mechanisms of orofacial deep-tissue pain is still unclear. Previously, P2X receptors (P2XR) in sensory neurons have been shown to play a role in the signal transduction of cutaneous pain. We investigated the functional significance of P2X3R in relation to orofacial deep-tissue pain caused by monoarthritis of the temporomandibular joint (TMJ). Monoarthritis was induced by the injection of complete Freund's adjuvant (CFA) into the unilateral TMJ of the rat. The pain associated with monoarthritis was assessed by the pressure pain threshold (PPT), which was defined as the amount of pressure required to induce vocalization. Fifteen days after CFA-treatment, changes in PPT were examined after injection of P2XR agonists or antagonists into the TMJ. The number of cells expressing P2X3R in trigeminal ganglia (TG) was investigated by immunohistochemistry. Inflamed TMJ showed a continuous decline in PPT during the experimental period (P<0.001). Injection of α,β-meATP, an agonist of P2X1,3,2/3R, dramatically reduced the bilateral PPTs of both inflamed and non-inflamed TMJs (P<0.01) although β,γ-me-L-ATP, a selective agonist of P2X1R, did not. The decreased PPTs of inflamed TMJ were reversed either by PPADS, an antagonist of P2X1,2,3,5,1/5,4/5R, or by TNP-ATP, an antagonist of P2X1,3,2/3,1/5R. Immunohistochemically, the number of P2X3R-positive cells increased in the small cell group in TG (P<0.01), whereas there was no change in medium or large cell groups after the CFA-injection. Retrograde tracing confirmed that TMJ neurons in the TG exhibited P2X3R immunoreactivity. Our results suggested that P2X3R plays an important role in orofacial pressure pain caused by monoarthritis of TMJ.
aDepartment of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya 466–8550, Japan
bDepartment of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya 466–8550, Japan
*Corresponding author. Tel.: +81 52 744 2014; fax: +81 52 744 2027.
Submitted June 29, 2004; revised March 8, 2005; accepted March 29, 2005.