Mechanisms underlying 5-HT-induced nociception in the TMJ

Objective: 5-hydroxytryptamine (5-HT) induces nociception by a norepinephrine-independent mechanism that involves neutrophil migration and local release of prostaglandin. We investigated whether 5-HT induces temporomandibular joint (TMJ) nociception in rats by mechanisms distinct to those mediating nociception in the subcutaneous tissue, Methods: The nociceptive behavioral responses characterized by rubbing the periarticular region and shaking the head were quantified for 45 minutes after TMJ treatments and taken together as a quantitative nociceptive behavioral measure(Roveroni et al., 2001). One-way ANOVA and Tukey test were used for statistical analysis (p<0.05), Results: TMJ injection of 5-HT (75, 225 or 450µg) induced a dose-dependent nociceptive behavior that was significantly reduced (p<0.05) by co-injection of the 5-HT3 receptor antagonist tropisetron (150µg; n=6; 50%), by TMJ injection of the cyclooxygenase inhibitor indomethacin (10, 30 or 100µg, 30 min prior to the TMJ injection of 5-HT; n=5; 60%), by guanethidine (30 mg/Kg sc., 3 days pretreatment; n=7) depletion of norepinephrine in the sympathetic terminals (60%), and by co-injection of the ß1 (0.5, 2.0 or 6.0µg, n=6) or ß2-adrenergic receptor antagonist (0.1, 0.5µg n=9, or 1.5µg, n=6) atenolol (60%) or ICI 118,551 (70%), respectively. The nonspecific selectin inhibitor fucoidan (20mg/Kg i.v., 20 min. pretreatment, n=6) did not affect 5-HT-induced nociception in the TMJ region, Conclusions: We conclude that the mechanism underlying 5-HT-induced nociception in the articular tissue of the TMJ resembles that of the subcutaneous tissue in that, like it, it is characterized by an indirect action of 5-HT on the primary afferent mediated by the local release of prostaglandin. However, important differences exist, that is, the mechanism underlying 5-HT- induced nociception in the articular tissue of the TMJ region but not in the subcutaneous tissue depends on norepinephrine but not on neutrophil migration.