Role of Neuron-Glial Interaction Mediated by IL-1β in Ectopic Tooth Pain. (April 2018)

• Record Type: Journal Article
• Authors: Komiya, H.; Shimizu, K.; Noma, N.; Tsuboi, Y.; Honda, K.; Kanno, K.; Ohara, K.; Shinoda, M.; Ogiso, B.; Iwata, K.
• Is Part Of: Journal of dental research. Volume 97:Number 4(2018)
• Page Start: 467
• Page End: 475
• Publication Date: 2018-04
• Subjects: facial pain -- endodontics -- pulpitis -- referred pain -- hyperalgesia -- trigeminal ganglion; Dentistry -- Periodicals; Dentistry -- Social aspects -- Periodicals; Dentistry -- Periodicals; Research -- Periodicals; 617.6005
• DOI: 10.1177/0022034517741253
• Languages: English
• ISSNs: 0022-0345

Abstract

Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar–innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)–labeled cells encircled by glial fibrillary acid protein–immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein–IR + IL-1β-IR cells, IL-1 type I receptor–IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1β mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.