Effect Of Neonatal Maternal Separation On Visceral Sensitivity Of Pain In Developing Rats And Role Of Fos Abnormal Expression In Spinal Cord

Objective: To explore the effect of maternal separation (MS) stimulation in neonatal period on visceral sensitivity of pain in developing rats by the method of behavior and electrophysiology research. Compareing Fos expression at dorsalhorn of lumbarsacral spinal cord of visceral hypersensibility in developing rats with control rats, in order to investigate the role of Fos abnormal expression in dorsal horn of spinal cord of visceral hyperalgesia in developing rats.Method: [1]20 SD neonatal rats were divided randomly into MS group (n=10) and control group (n=10). Rats in MS group were separated from the dam for 3h/d (8:00-11:00am) on postnatal days 2～14 for 13 consecutive days, rats in control group were not treated and remained in the home cage with the dam. Conventionally breeding to the young period (6-week age), observing the score of abdominal withdrawal reflex (AWR),visceral pain threshold and measurement of electrical discharge of external oblique muscle of abdomen (EOMA) under different pressures of colorectal distension (CRD) irritation to evaluate visceral algesthesia in rats. Select descending colon to do patholigical examination. [2]According to the factorial design, 32 SD rats were divided into four groups with each 8, Group A was MS group and not imposed on CRD at 6-week age, yet Group B was imposed on CRD as MS group. Group C was imposed on CRD at 6-week age while Group D without treatment both as control group. On the 6th week, after the rats of Group B and C were imposed on CRD for 2 hours while rats of Group A and D not imposed on CRD were sampled the spinal cord from L6 to S2, the semi-quantity analysis of staining density and the cell numbers of Fos-Like Immunoreactivity (FLI) of spinal cord were made through immunohisrochemical coloration and computer image analyzing system. SPSS 11.0 software for Windows was used in all statistical tests.α=0.05 was considered significant.Result: [1]The AWR scores increased gradually with the rising of the CRD pressure in developing rats; neonatal MS and gender had effect on the AWR scores (F was 26.53,9.24 respectively, p<0.001), The AWR scores were obviously higher in female than male rats, and the AWR scores were obviously higher in MS than control rats, there was no interaction between MS and gender on affecting the AWR scores (F =0.97, p=0.339); When the CRD pressures were20mmHg,40mmHg,60mmHg, the AWR scores were higher in MS than control rats signigficantly. But when pressure reached 80 mmHg, there was no significant difference of the AWR scores between two gruops. The Pain Thresholds of MS and control rats(?x±s ) were 17.67±8.2mmHg,33.83±4.3mmHg respectively (F=30.415, p<0.01). [2] With the CRD pressure increased, The amplitudes of spike of EOMA increased too; neonatal MS and gender had effect on the spikes of EOMA (F was 18.83,7.62 respectively, p<0.05 ), the spikes of EOMA were obviously higher in female than male rats, and the spikes of EOMA were higher in MS than control rats, When the CRD pressures were 15mmHg,30mmHg and 45mmHg, the spikes of EOMA were higher in MS than control rats signigficantly. But when pressures were 60mmHg,75mmHg, the differences were no statistical significance. There were no significant differences of weight between two groups and there were no obvious histopatholigical changes in descending colon in MS and control rats. [3]Rats accepted MS in neonatal period and CRD at 6-week age both could make the number of FLI increase and staining density of FLI decrease significantly in lumbosacral spinal dorsal horn, the differences had statistical significance. There was not interaction between MS and CRD on affecting the number and staining density of FLI.Conclusion: The persistent MS in neonatal phase can cause primary central sensitization of spinal cord in developing rats. Accepting detrimental CRD can significantly cause the high expression of Fos in spinal cord and result in decreasing of pain threshold in rats, emerging chronic visceral hyperalgesia. This hyperalgesia can continue to juvenile stage and there is no histological change found in colorectal tissues.