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.

Comparative study of electroacupuncture and moxibustion in influencing Tianshu(ST 25) regions mast cells in visceral hyperalgesia rats

Objective：To evaluate and compare electroacupunctures（EA） with different parameters and moxibustion at different temperatures influencing the activation of mast cells（MC） in Tianshu（ST 25） regions of visceral hyperalgesia model rats.Methods：Rats（except for model group） respectively accepted 1 m A or 3 m A EA or moxibustion at 43 or 4 to ℃ ℃stimulate Tianshu（ST 25） points after randomization of the fifty visceral hyperalgesia model rats,and then were compared with that in model and normal groups.Number,degranulation numbers,degranulation rates in Tianshu（ST 25） regions MC of rats in each group were observed using toluidine blue staining.Abdominal withdrawl reflex（AWR） score was used to evaluate the rat visceral hyperalgesia reactions.Results：Compared with the normal group and the model group,MC numbers（P〈0.05,P〈0.01,P〈0.01,P〈0.01）,degranulation numbers and degranulation rates（P〈0.01,P〈0.01,P〈0.05,P〈0.01） of Tianshu（ST 25） MC in regions tissues in 43 and 4 moxibustion groups,and 1 m A and 3 m℃ ℃A EA groups all increased significantly.Compared with the model group,AWR scores were significantly lower in 43 and 4 ℃ moxibustion groups,and 1 m A and 3 m℃A EA groups under the stimulation of 20 mm Hg,40 mm Hg,0 mm Hg or 80 mm Hg colorectal distension（CRD）（P〈0.05 in 1 m A and 3 m A EA groups under the stimulation of 20 mm Hg,P〈0.01 in the other groups）.AWR scores in 43 ℃and 4 ℃moxibustion groups under the stimulation of 20 mm Hg,40 mm Hg,0 mm Hg or 80 mm Hg CRD were not significantly different from those in the normal group（all P〈0.05）;AWR scores in 1 m A EA group under the stimulation of 0 mm Hg or 80 mm Hg were significantly higher than that in the normal group（P〈0.01）;AWR score in 3 m A EA group under the stimulation of 0 mm Hg was significantly higher than that in the normal group（P〈0.01）,and AWR scores in 3 m A EA group under the stimulation of 20 mm Hg or 80 mm Hg were also higher than that in the normal group（P〈0.05）.AWR scores were higher in 1 m A EA group under the stimulation of 40 mm Hg or 80 mm Hg than that in 4 moxibustion group（℃ P〈0.05）;AWR score was higher in 3 m A EA group under the stimulation of 40 mm Hg than that in 4 moxibustion group（℃ P〈0.05）.Conclusion：There are differences among EA of different parameters and moxibustion of different temperatures in activating on Tianshu（ST 25） regions MC of visceral hyperalgesia model rats,as well as in improving the visceral hyperalgesia reaction.The effect of 4 moxibustion℃ is the most significant.

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.

Irritable bowel syndrome:The evolution of multi-dimensional looking and multidisciplinary treatments

Irritable bowel syndrome(IBS)is common in the society.Among the putative pathogeneses,gut dysmotility results in pain and disturbed defecation.The latter is probably caused by the effect of abnormal gut water secretion.The interaction between abnormal gas accumulation,abdominal pain and bloating remains controversial.Visceral hypersensitivity and its modification along with the central transmission are the characteristics of IBS patients.The identification of biologic markers based on genetic polymorphisms is undetermined.Imbalanced gut microbiota may alter epithelial permeability to activate nociceptive sensory pathways which in turn lead to IBS.Certain food constituents may exacerbate bowel symptoms.The impact of adult and childhood abuses on IBS is underestimated.Using the concept of biopsychosocial dysfunction can integrate multidimensional pathogeneses.Antispasmodics plus stool consistency modifiers to treat the major symptoms and defecation are the first-line drug treatment.New drugs targeting receptors governing bowel motility,sensation and secretion can be considered,but clinicians must be aware of their potential serious side effects.Psychiatric drugs and modalities may be the final options for treating intractable subjects.Probiotics of multi-species preparations are safe and worth to be considered for the treatment.Antibiotics are promising but their longterm safety and effectiveness are unknown.Diet therapy including exclusion of certain food constituents is an economic measure.Using relatively safe complementary and alternative medicines(CAMs)may be optional to those patients who failed classical treatment.In conclusion,IBS is a heterogeneous disorder with multidimensional pathogeneses.Personalized medicines with multidisciplinary approaches using different classes of drugs,psychiatric measures,probiotics and antibiotics,dietary therapy,and finally CAMs,can be considered.