Anxiety Promotes Occlusal Interference-Induced Myalgia via the Mesolimbic System

Acute occlusal interference may induce chronic masticatory myalgia in some individuals. The potential factors and underlying mechanisms that predispose one to occlusion-related masticatory myalgia remain unclear. Anxiety has been shown to facilitate pain perception. The ventral tegmental area, a critical component of the mesolimbic dopamine circuit, is involved in the neural networks shared by anxiety and pain. Whether anxiety levels influence masticatory myalgia induced by occlusal interference and what role the ventral tegmental area plays in this interaction have yet to be fully elucidated. In this study, we quantified the inborn variability in anxiety levels of male Sprague-Dawley rats using the elevated plus maze. We observed that high anxiety levels enhanced mechanical hypersensitivity in masseter muscle following application of experimental occlusion interference. Immunofluorescence and in vivo electrophysiologic experiments revealed differences in the activity of dopaminergic neurons and low-frequency oscillations in the ventral tegmental area of rats with varying anxiety levels following occlusion interference. Chemogenetic manipulations of dopaminergic neurons in the ventral tegmental area influenced the facilitatory effect of anxiety on occlusion interference-induced masseteric hyperalgesia. These findings provide the first evidence that anxiety can facilitate occlusion interference-induced masticatory myalgia, with the ventral tegmental area playing a crucial role in this neurobiological process.