• Peng Zhang and Ye-Hua Gan.
• Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.
• Inflammation. 2017 Jun 1; 40 (3): 1102-1109.

AbstractProstaglandin E2 (PGE2) is a key proinflammatory mediator that contributes to inflammatory hyperalgesia. Voltage-gated sodium channel 1.7 (Nav1.7) plays an important role in inflammatory pain. However, the modulation of Nav1.7 in inflammatory pain remains poorly understood. We hypothesized that PGE2 might regulate Nav1.7 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 Nav1.7 through PGE2 receptor EP2. This finding was confirmed by studies on EP2-selective antagonist PF-04418948. We also demonstrated that Nav1.7 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 Nav1.7 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 Nav1.7 expression to contribute to TMJ inflammatory pain in rats. Our finding suggests that PGE2 was an important regulator of Nav1.7 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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