Effects Of Intrathecal TRPV1 Receptor Antagonist On The Nociceptive Response To The Visceral Pain Induced By Uterine Cervical Distension In A Rat Model

Background:Labor pain is a typical acute visceral pain,severe labor pain can cause a series of adverse effects on the mother and fetus.The mechanism of Labor pain is very complicated.Its detailed mechanism is still unkown.Studies have shown that cervical mechanical distension is the main source of labor pain.TRPV1 is a non-selective ligand-gated cation channel that plays an important role in the transduction of mechanical stimulation.Recent studies have found that TRPV1 is highly expressed in the uterus and cervix,which may play a role in the afferent and transduction of noxious cervical distension stimulation during delivery.However,the effect of TRPV1 on the development of uterine cervical distension pain still needs further confirmation.Objection:To observe the effects of intrathecal TRPV1 receptor antagoniston the changes of heart rate,rectus abdominis EMG and the cFos expression inT12-L2 spinal cord induced by uterine cervical distension in a rat model,and then investigate its role and the possible mechanism of modulating pain in uterine cervical distension.Materials and Method:Sprague-Dawley adult virgin female rats 3 borned 8 to 10 weeks,weighing 180 to 220 g,were taken for a operation of intrathecal catheter.24 of the rats which were survived the intrathecal catheterization were randomly divided into 4 groups(n=6):control group(group C)、group of uterine cervical distension(UCD)(group U)、group of TRPV1 receptor antagonist intrathecally injected before UCD with 75 g weights(group C+U)and group of vehicle intrathecally injected before UCD with 75 g weights(group D+U).The group C just had a sham operation of UCD without any weights and nothing intrathecally injected before UCD.Half an hour before UCD with 75 g weights,the group U were were treated nothing intrathecally,while the group C+D were intrathecally injected with 10μL TRPV1 receptor antagonist Capsaizepine(20μg,2mg/ml dissolved in 10%DMSO solution)and the group D+U were intrathecally injected of lOμL 10%DMSO solution.Each distension lasted for 1 hour and then recoverd for 30 minutes.Heart rate was monitored and recorded,and EMG signals were monitored using the Medlab-U/4C biosignal system.Immediately after the end of the experiment,T12-L2 spinal cord segments were taken for immunofluorescence staining,and the distribution of cFos protein in the T12-L2 spinal cord was observed under an optical microscope and counted.Results:Compared with group C,the heart rate of the group U was increased after uterine cervical distension(P<0.01),the rectus abdominis EMG activity and cFos expression in the spinal cord significantly increased(P<0.001).There was no significant difference in heart rate,rectus abdominis EMG activity and cFos expression between group D+U and group U(P>0.05).While the heart rate,the rectus abdominis EMG activity and the cFos expression of group C+U were both decreased significantly after uterine cervical distension(P<0.01)compared with group U.Conclusions:Intrathecal injected TRPV1 receptor antagonist can reduce visceral pain responses induced by uterine cervical distension in rats.TRPV1 receptor is involved in the formation of acute uterine cervical distension pain.