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Prostaglandin E2 Upregulated Trigeminal Ganglionic Sodium Channel 1.7 Involving Temporomandibular Joint Inflammatory Pain in Rats

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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 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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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81271173) and China International Science and Technology Cooperation (Grant No. 2013DFB30360).

Authors’ Contributions

YHG designed the study, analyzed the data, and wrote the manuscript. PZ conducted the study, analyzed the data, and wrote the manuscript. Both authors read and approved the final manuscript.

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Authors and Affiliations

  1. Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

    Peng Zhang & Ye-Hua Gan

  2. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

    Peng Zhang & Ye-Hua Gan

  3. Center for TMD and Orofacial Pain, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

    Ye-Hua Gan

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  1. Peng Zhang
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Correspondence to Ye-Hua Gan.

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The experimental protocols utilized in the study were approved by the Animal Use and Care Committee of Peking University. The employed procedures were also consistent with the Ethical Guidelines of the International Association for the Study of Pain.

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The authors declare that they have no competing financial interests.

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Zhang, P., Gan, YH. Prostaglandin E2 Upregulated Trigeminal Ganglionic Sodium Channel 1.7 Involving Temporomandibular Joint Inflammatory Pain in Rats. Inflammation 40, 1102–1109 (2017). https://doi.org/10.1007/s10753-017-0552-2

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