Roles Of Spinal P38MAPK In Chronic Visceral Pain

ObjectiveThe roles of spinal P38 MAPK in rats with chronic functional visceral pain was explored in order to deeply clarify the pathogenesis of chronic functional visceral pain,which could supply a new thought and target point for its pharmacotherapy.Methods(1)Rat model of irritable bowel syndrome(IBS): the 60 mmHg colorectal dilatation was given for 1min at the same time once a day during post-natal days 8-14.The controls were treated in the same way except for neonatal colorectal dilatation(NCI).The visceral hypersensitivity was assessed by recording the responses of the external oblique abdominal muscle to colorectal distention(CRD,40 and 60 mmHg)when they were adult(8 weeks).(2)The expression of P38 MAPK and phosphorylated P38MAPK(P-P38MAPK)of spinal thoracolumbar(TL)and lunbosacral(LS)segments were detected by western blot and immunohistochemistry.(3)The effects of SB203580(A P38 MAPK inhibitor)on visceral hypersensitivity were examined by the response of EMG after intrathecal administration.(4)The expressions of spinal BDNF were compared between pre-administration and post-administration of SB203580 by Western Blot.(5)Effects of SB203580 on movement and emotion were examined by Open field test.Results(1)The amplitude ratios of EMG to CRD were significantly increased in IBS rats when compared with control rats(p<0.05).(2)Data of Western blot and immunehistochemistry indicated that expression of TL and LS P-P38 MAPK significantly enhanced in IBS rats when compared with control rats(p<0.05).There was no significant difference on expression of TL and LS P38 MAPK between the control and IBS rats.Immunohistochemical staining of P38 MAPK and P-P38 MAPK in Spinal dorsal horn were tan.P38 MAPK are mainly in the cytoplasm,P-P38 MAPK are mainly expressed in the nucleus.(3)Intrathecal administration of SB203580 significantly inhibited pain sensitivity in a dose-dependent way in IBS rats(p<0.05).(4)The expression of spinal TL and LS BDNF was significantly decreased after intrathecal injection of SB203580(p<0.05).Open fiel(5)d test showed that the ratio of central time to total time and central distance to total distance were significantly decreased(p<0.05)after intrathecal administration of SB203580,but there was no significant difference in the total walking distance and average speed of between pre-administration and post-administration of SB203580.ConclusionNeonatal colorectal dilatation leads to the formation of chronic visceral hypersensitivity when grown up in SD rats.P38 MAPK phosphorylation cause the release of BDNF in spinal TL and LS may be the mechanism for the formation of chronic visceral pain on IBS.