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.