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Effects of serotonin on the excitability and mechanical thresholds of masticatory muscle afferent fibre Sung, David


Recent human clinical evidence suggests a relationship between intramuscular (IM) serotonin (5-HT) levels and chronic masticatory muscle pain associated with temporomandibular disorders (TMDs) and fibromyalgia (FM). Further, human experimental pain studies have demonstrated that injection of 5-HT into masticatory muscle causes modest, short-lived pain and a longer-lasting mechanical sensitization that appear to be mediated by activation of peripheral 5-HT3 receptors. However, it has not yet been clearly delineated what 5-HT₃ receptor types are expressed by sensory (afferent) fibres that innervate masticatory muscle. Also, it is not known what types of muscle afferent fibres 5-HT excites or sensitizes. In this study, immunohistochemistry techniques were used to determine the frequencies of expression of the 5-HT₁, 5-HT₂, and 5-HT₃ receptors by rat masticatory muscle ganglion cells. Electrophysiology experiments were carried out to determine the effects of repeated IM injection of 5-HT (0.1, 1, or 10 mM) on the excitability and mechanical thresholds of rat masticatory muscle afferent fibres. An electronic Von Frey Hair was used to measure afferent fibre mechanical thresholds before the initial and 10 min after the second IM injection. Our immunohistochemistry results suggest that 5-HT₁B[subscript] and especially 5-HT₁A[subscript] receptors, owing to their low frequencies of expression, may play minor roles in peripheral nociceptive transduction in uninflamed muscle tissue. In contrast, 5-HT₃ receptors, which are relatively highly expressed, likely play a more prominent role in peripheral nociception. Our electrophysiology results demonstrate that IM injection of 5-HT evokes rapid, relatively reproducible and concentration-dependent increases in afferent fibre excitability that are mediated, at least in part, by a peripheral receptor mechanism involving the 5-HT₃ receptor. However, IM injection of 5-HT did not significantly sensitize putative muscle afferent fibres to mechanical stimuli. We unexpectedly found that IM injection of 5-HT resulted in a marked decrease in blood pressure, a phenomenon that has yet to be explained. These findings indicate that 5-HT excites putative nociceptive afferent fibres that innervate masticatory muscle through activation of peripheral 5-HT₃ receptors, which suggests that the peripheral 5-HT₃ receptor may be an important target for future analgesic drugs.

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