PAR 2 and temporomandibular joint inflammation in the rat

The proteinase-activated receptor 2 (par2) is a putative therapeutic target for arthritis. we hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (tmj) are mediated by neurogenic mechanisms. immunofluorescence analysis revealed a high degree of neurons expressing par2 in retrogradely labeled trigeminal ganglion neurons. furthermore,par2 immunoreactivity was observed in the lining layer of the tmj,co-localizing with the neuronal marker pgp9.5 and substance-p-containing peripheral sensory nerve fibers. the intra-articular injection of par2 agonists into the tmj triggered a dose-dependent increase in plasma extravasation,neutrophil influx,and induction of mechanical allodynia. the pharmacological blockade of natural killer 1 (nk1) receptors abolished par2-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. we conclude that par2 activation is proinflammatory in the tmj,through a neurogenic mechanism involving nk1 receptors. this suggests that par2 is an important component of innate neuro-immune response in the rat tmj. © 2010 international & american associations for dental research.