Mild moxibustion at Tianshu (ST 25) decreases expression of prokineticin-1 and prokineticin receptor-1 in colon tissue of rats with chronic visceral hyperalgesia

Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu （ST 25） decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.

Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats

AIM:To investigate the pharmacological effect of JCM-16021,a Chinese herbal formula,and its underlying mechanisms.METHODS:JCM-16021 is composed of seven herbal plant materials.All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia(2005).In a neonatal maternal separation(NMS)model,male SpragueDawley rats were submitted to daily maternal separation from postnatal day 2 to day 14,or no specific handling(NH).Starting from postnatal day 60,rats were administered JCM-16021(2,4,8 g/kg per day)orally twice a day for 28 d.Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System(AD Instruments International),were tested as pain indices.Changes in serotonin(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)concentrations in the colon of rats were analyzed;the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method.RESULTS:NMS treatment significantly reduced pain threshold pressure(37.4±1.4 mmHg),as compared to that of NH rats(57.7±1.9 mmHg,P<0.05).After JCM-16021 treatment,the pain threshold pressure significantly increased when compared to that before treatment(34.2±0.9 mmHg vs 52.8±2.3 mmHg in the high dose group,40.2±1.6 mmHg vs 46.5±1.3 mmHg in the middle dose group,and 39.3±0.7 mmHg vs 46.5±1.6 mmHg in the low dose group,P<0.05).Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension(CRD),(the meanΔAUC values were:0.17±0.03,0.53±0.15,1.06±0.18,1.22±0.24 in the high dose group;0.23±0.04,0.68±0.17,1.27 ±0.26,1.8±0.3 in the middle dose group;and 0.29 ±0.06,0.8±0.16,1.53±0.24,2.1±0.21 in the low dose group for the pressures 20,40,60,80 mmHg),as compared to the NMS vehicle group.The meanΔAUC values were:0.57±0.12,1.33±0.18,2.57±0.37,3.08±0.37 for the pressures 20,40,60,80 mmHg(P <0.05).JCM-16021 treatment significantly reduced the 5-HT concentrations(from high,middle and low dosage groups:60.25±5.98 ng/100 mg,60.32±4.22 ng/100 mg,73.31±7.65 ng/100 mg),as compared to the NMS vehicle groups(93.11±9.85 ng/100 mg,P<0.05);and increased the 5-HIAA concentrations(after treatment,from high,middle and low dosage groups:54.24±3.27 ng/100 mg,50.34±1.26 ng/100 mg,51.37±2.13 ng/100 mg)when compared to that in the NMS vehicle group(51.75±1.98 ng/100 mg,P <0.05);but did not change the enterochromaffin cell numbers in the colon of rats.In addition,NMS rats had higher SERT expression(n=10)than NH rats(n=8,P<0.05).JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group(P <0.01-0.001).CONCLUSION:JCM-16021 can attenuate visceral hypersensitivity,and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats.