title: Prostanoid-dependent spontaneous pain and PAR2-dependent mechanical allodynia following oral mucosal trauma: involvement of TRPV1, TRPA1 and TRPV4.
abstract: During dental treatments, intraoral appliances frequently induce traumatic ulcers in the oral mucosa. Such mucosal injury-induced mucositis leads to severe pain, resulting in poor quality of life and decreased cooperation in the therapy. To elucidate mucosal pain mechanisms, we developed a new rat model of intraoral wire-induced mucositis and investigated pain mechanisms using our proprietary assay system for conscious rats. A thick metal wire was installed in the rats between the inferior incisors for one day. In the mucosa of the mandibular labial fornix region, which was touched with a free end of the wire, traumatic ulcer and submucosal abscess were induced on day 1. The ulcer was quickly cured until next day and abscess formation was gradually disappeared until five days. Spontaneous nociceptive behavior was induced on day 1 only, and mechanical allodynia persisted over day 3. Antibiotic pretreatment did not affect pain induction. Spontaneous nociceptive behavior was sensitive to indomethacin (cyclooxygenase inhibitor), ONO-8711 (prostanoid receptor EP1 antagonist), SB-366791, and HC-030031 (TRPV1 and TRPA1 antagonists, respectively). Prostaglandin E2 and 15-deoxyΔ12,14-prostaglandin J2 were upregulated only on day 1. In contrast, mechanical allodynia was sensitive to FSLLRY-NH2 (protease-activated receptor PAR2 antagonist) and RN-1734 (TRPV4 antagonist). Neutrophil elastase, which is known as a biased agonist for PAR2, was upregulated on days 1 to 2. These results suggest that prostanoids and PAR2 activation elicit TRPV1- and TRPA1-mediated spontaneous pain and TRPV4-mediated mechanical allodynia, respectively, independently of bacterial infection, following oral mucosal trauma. The pathophysiological pain mechanism suggests effective analgesic approaches for dental patients suffering from mucosal trauma-induced pain.
authors.affiliation: Kyushu Shika Daigaku.
authors.forename: Misa
authors.initials: M
authors.lastname: Ito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Kyushu Shika Daigaku.
authors.forename: Suzuro
authors.initials: S
authors.lastname: Hitomi
authors.affiliation: Kyushu Shika Daigaku.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Nodai
authors.affiliation: Kyushu Shika Daigaku.
authors.forename: Teppei
authors.initials: T
authors.lastname: Sago
authors.affiliation: Kyushu Shika Daigaku.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Kyushu Dental University.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Harano
authors.affiliation: Kyushu Dental　University.
authors.forename: Kaori
authors.initials: K
authors.lastname: Gunnjigake
authors.affiliation: Kyushu Dental University.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hosokawa
authors.affiliation: Kyushu Dental University.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Kyushu Dental University.
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Inenaga
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D010146:Pain / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D000074025:TRPA1 Cation Channel / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D001643:Bridged Bicyclo Compounds; D002208:Caproates; C122148:ONO 8711; D011453:Prostaglandins; D011687:Purines; C544743:RN 1734; D044464:Receptor, PAR-2; D013449:Sulfonamides; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; C486577:Trpv4 protein, rat