title: Prostaglandin E2Upregulated 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 (Nav1.7) plays an important role in inflammatory pain. However, the modulation of Nav1.7 in inflammatory pain remains poorly understood. We hypothesized that PGE2might regulate Nav1.7 expression in inflammatory pain. We here showed that treatment of rat trigeminal ganglion (TG) explants with PGE2significantly upregulated the mRNA and protein expressions of Nav1.7 through PGE2receptor 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 PGE2levels, 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 PGE2levels 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 PGE2upregulated trigeminal ganglionic Nav1.7 expression to contribute to TMJ inflammatory pain in rats. Our finding suggests that PGE2was 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.
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.|Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China. kqyehuagan@bjmu.edu.cn.|Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China. kqyehuagan@bjmu.edu.cn.|Center for TMD and Orofacial Pain, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China. kqyehuagan@bjmu.edu.cn.
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D007249:Inflammation; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D010146:Pain; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000473:pathology*; D012668:Trigeminal Ganglion / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C503480:Scn9a protein, rat; D015222:Sodium Channels; D015232:Dinoprostone
keywords: inflammatory pain; prostaglandin E2; sodium channel 1.7; temporomandibular joint; trigeminal ganglion