Estrogen-dependent effects of vagotomy and endogenous opioids on temporomandibular joint-responsive neurons in trigeminal subnucleus caudalis

Temporomandibular joint (TMJ) disorders are common orofacial pain conditions influenced by multiple factors. This study examined how vagotomy and endogenous opioids affect TMJ-responsive neurons in the trigeminal subnucleus caudalis/cervical junction (Vc/C_1-2) in female rats under different estrogen levels. Under low estrogen, cervical vagotomy enhanced TMJ unit responses to levels seen in high estrogen conditions but had no additional effect under high estrogen. Vagotomy did not change chemical stimulation (ATP) thresholds or spontaneous activity, suggesting a central neural mechanism. Responses to mechanical stimulation of the skin over the TMJ were unaffected. Naloxone increased ATP-evoked responses under low estrogen but had no added effect after vagotomy or under high estrogen. Naloxone also did not alter spontaneous activity or mechanical responses. These findings indicate that vagal input and endogenous opioids significantly modulate TMJ neuron activity under low estrogen, while high estrogen levels limit further excitation, implying estrogen-dependent regulation of vagus and opioid effects on Vc/C_1-2 neurons.