Locus coeruleus activation contributes to masseter muscle overactivity induced by chronic restraint stress in mice

It is commonly accepted that exposure to stress may cause overactivity in the orofacial muscles, leading to consistent muscle pain, which is the main symptom of temporomandibular disorders. The central neural mechanism underlying this process, however, remains unclear. The locus coeruleus is considered to play an important role in stress-related behavioral changes. Therefore, the present study was designed to examine the role of locus coeruleus neurons in masseter overactivity induced by stress. C57BL/6 mice were subjected to chronic restraint stress for 14 days to establish an animal model. The behavioral changes and the electromyography of the masseter muscle in mice were measured. The expression of Fos in locus coeruleus was observed by immunofluorescence staining to assess neuronal activation. A chemogenetic test was used to inhibit locus coeruleus neuronal activity, and the behavioral changes and electromyography of the masseter muscle were observed again. The results exhibited that chronic restraint stress could induce anxiety-like behavior, overactivity of the masseter muscle, and significant activation of locus coeruleus neurons in mice. Furthermore, inhibition of noradrenergic neuron activity within the locus coeruleus could alleviate stress-induced anxiety behavior and masseter muscle overactivity. Activation of noradrenergic neurons in locus coeruleus induced by stress may be one of the central regulatory mechanisms for stress-induced anxiety-like behaviors and overactivity of masseter muscles.