Lamotrigine reverses masseter overactivity caused by stress maybe via Glu suppression

Abstract

Experimental and non-experimental stress significantly increase masseter muscle tone, which has been linked to the symptoms and pathogenesis of several stomatognathic system diseases. Until now, the mechanism underlying this phenomenon has remained unclear. The current study was performed to determine the mechanism of the stress-induced increase in masseter muscle tone and to investigate the effect of lamotrigine on this change. Animals challenged by repeated restraint stress received either saline as a vehicle or lamotrigine in doses of 20, 30 or 40 mg/kg body weight, whereas control animals received saline without stress treatment. Masseter muscle tone was assessed using electromyography. The activity of glutamate-related metabolic enzymes (glutaminase and glutamine synthetase) in the trigeminal motor nucleus was also investigated. Our results showed an interesting phenomenon: masseter muscle activity increased concurrently with the upregulation of the glutamate concentration after stress treatment. The activities of glutaminase and glutamine synthetase in the trigeminal motor nucleus were also upregulated and downregulated, respectively, when the rats were challenged by prolonged stress. The animals treated with lamotrigine at moderate and high doses had significantly decreased masseter muscle tone compared with stressed animals treated with vehicle. These results suggested that increased glutaminase activity and decreased glutamine synthetase activity increased glutamate production and decreased glutamate decomposition, causing an increase in glutamate levels in the trigeminal motor nucleus and eventually increasing masseter muscle tone. The administration of lamotrigine at doses of 30 or 40 mg/kg body weight effectively mitigated the adverse effects of stress on masseter muscle tone via inhibition of glutamate release.

Keywords: Chronic restraint stress; Glutamate; Lamotrigine; Masseter; Muscle tone; Trigeminal motor nucleus.