Study On The Changes And Mechanism Of Oral And Facial Pain And Temperature Perception Under Low Estrogen Condition

Objective:In this study,we aimed to investigate changes in vesicular glutamate transporter 2(Vglut2)and vesicular GABA transporter(Vgat1)expression in the trigeminal ganglion,caudal subnucleus of the trigeminal spinal tract nucleus,lateral parabrachial nucleus,ventroposterior medial nucleus of the subthalamus,as well as changes in orofacial temperature and mechanical pain thresholds in the hypoestrogenic state,so as to explore the effect of estrogen on the expression of glutamate and GABA neurons in oral and facial pain temperature perception pathway.And the effect on the threshold and temperature of oral and facial pain Methods:In this study,24 adult female SD rats were randomly divided into sham operation(SHAM)group,ovariectomized(OVX)group and estrogen treatment(OVX+E)group with 8 rats in each group.Bilateral ovariectomy was performed in OVX group and OVX+E group.2 weeks after operation,rats in OVX+E group were treated with subcutaneous estrogen in groin,SHAM and OVX group were treated with subcutaneous sesame oil(estrogen solvent)for 6 weeks.The success of the ovariectomized rat model was determined by observing the smear of vaginal exfoliated cells and the morphology of uterus.The distribution and expression of glutamatergic neuron specific marker Vglut2 and GABA neuron specific marker Vgat1 in the trigeminal ganglion,caudal subnucleus of spinal trigeminal nucleus,lateral parabrachial nucleus and ventral posteromedial nucleus of thalamus were observed by immunohistochemistry and Western Blot.Von Frey fiber mechanical stimulation needle was used to detect the threshold of oral and facial shrinking,and infrared thermal imaging was used to monitor the temperature change of oral and facial temperature of rats.Results:After ovariectomy,there was no estrous cycle in rats,and the weight increased and the shape of uterus atrophied obviously,which could be corrected by estrogen treatment.Vglut2,a marker of glutamatergic neurons,and Vgat1,a marker of GABA neurons,are expressed in trigeminal ganglion,caudal subnucleus of trigeminal spinal nucleus,lateral parabrachial nucleus and ventral posteromedial nucleus of thalamus.Ovariectomy can lead to changes in the expression levels of Vglut2 and Vgat1.The expression of Vglut2 and Vgat1 in peripheral trigeminal ganglion and caudal subnucleus of trigeminal nucleus showed a downward trend,and the decrease of Vgat1 was greater than that of Vglut2.The expression of Vglut2 and Vgat1 increased in lateral parabrachial nucleus and ventral posteromedial nucleus of thalamus,and the increase of Vglut2 was greater than that of Vgat1.Under the condition of low estrogen,the mechanical pain threshold of the mouth and face decreased significantly,and the temperature of the mouth and face increased significantly.These changes can be corrected after estrogen supplementation.Conclusion:In the present experiment,ovariectomized rats successfully simulated the perimenopausal hypoestrogenic state.It is likely that perimenopausal hypoestrogenism affects the neurotransmission function of these two classes of neurons by affecting the number and proportion of glutamatergic and GABAergic neurons on the orofacial sensory information transduction pathway,leading to a dysregulation of glutamatergic and GABAergic neurons on the conduction pathway,Dysregulation of the balance of these two types of neurons may be a key contributor to perimenopausal orofacial dysesthesia.