Serotonin (5-HT) excites rat masticatory muscle afferent fibers through activation of peripheral 5-HT₃ receptors

Abstract 

In the present study, we combined immunohistochemical experiments with in vivo single unit recordings to examine whether 5-HT₃ receptors are expressed by masticatory (masseter and temporalis) sensory ganglion neurons and to investigate the effects of intramuscular injection of 5-HT on the excitability and mechanical threshold of rat masticatory muscle afferent fibers. The expression of 5-HT₃ receptors by masticatory ganglion neurons was examined using immunohistochemical techniques. In vivo extracellular single unit recording techniques were used to assess changes in the excitability of individual masticatory muscle afferent fibers. Immunohistochemical experiments detected a relatively high frequency (52%) of 5-HT₃ receptor expression by masticatory ganglion neurons. Injection of 5-HT (10⁻⁴, 10⁻³, 10⁻²M) evoked concentration-related increases in the magnitude of afferent discharge, but did not significantly sensitize muscle afferent fibers to mechanical stimuli. No significant sex-related differences in 5-HT-evoked afferent discharge were identified. Afferent discharge evoked by 5-HT was significantly attenuated by co-injection with the selective 5-HT₃ receptor antagonist tropisetron (10⁻³M). Afferent discharge was also evoked by the selective 5-HT₃ receptor agonist 2-methyl-5-HT. Unexpectedly, a significant concentration-related decrease in median blood pressure in response to 5-HT injection was found. This 5-HT-induced decrease in blood pressure was not antagonized by tropisetron or mimicked by 2-methyl-5-HT, indicating that the drop in blood pressure was not 5-HT₃ receptor-mediated. The present results indicate that 5-HT excites slowly conducting masticatory muscle afferent fibers through activation of peripheral 5-HT₃ receptors, and suggest that similar mechanisms may contribute to 5-HT-evoked muscle pain in human subjects.

Keywords: Mechanical threshold, Myofascial TMD pain, Masseter muscle, Orofacial pain, Temporalis muscle, Tropisetron