Prostaglandin E 2 Upregulated Trigeminal Ganglionic Sodium Channel 1.7 Involving Temporomandibular Joint Inflammatory Pain in Rats

Abstract

Prostaglandin E₂ (PGE₂) is a key proinflammatory mediator that contributes to inflammatory hyperalgesia. Voltage-gated sodium channel 1.7 (Na_v1.7) plays an important role in inflammatory pain. However, the modulation of Na_v1.7 in inflammatory pain remains poorly understood. We hypothesized that PGE₂ might regulate Na_v1.7 expression in inflammatory pain. We here showed that treatment of rat trigeminal ganglion (TG) explants with PGE₂ significantly upregulated the mRNA and protein expressions of Na_v1.7 through PGE₂ receptor EP2. This finding was confirmed by studies on EP2-selective antagonist PF-04418948. We also demonstrated that Na_v1.7 and COX-2 expressions, as well as PGE₂ levels, were upregulated in the TG after induction of rats' temporomandibular joint (TMJ) inflammation. Correspondingly, hyperalgesia, as indicated by head withdrawal threshold, was observed. Moreover, TMJ inflammation-induced upregulation of Na_v1.7 expression and PGE₂ levels in the TG could be reversed by COX-2-selective inhibitor meloxicam given by oral gavage, and meanwhile, the hyperalgesia of inflamed TMJ was also mitigated. So we concluded that PGE₂ upregulated trigeminal ganglionic Na_v1.7 expression to contribute to TMJ inflammatory pain in rats. Our finding suggests that PGE₂ was an important regulator of Na_v1.7 in TMJ inflammatory pain, which may help increase understanding on the hyperalgesia of peripheral inflammation and develop a new strategy to address inflammatory pain.

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