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

Abstract

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 Sprague-Dawley 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 mean DeltaAUC 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 mean DeltaAUC 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.

• Authors: Zhao-Xiang Bian, Man Zhang, Quan-Bin Han, Hong-Xi Xu, Joseph J Y Sung
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 16 Issue 7 Pg. 837-45 (Feb 21 2010) ISSN: 2219-2840 [Electronic] United States
• PMID: 20143462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Drugs, Chinese Herbal
• JCM-16021
• Serotonin Plasma Membrane Transport Proteins
• Slc6a4 protein, rat
• Serotonin
• Hydroxyindoleacetic Acid

Topics

• Administration, Oral
• Analgesics (administration & dosage, pharmacology)
• Animals
• Animals, Newborn
• Anxiety, Separation (complications, psychology)
• Colon (innervation, metabolism, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage, pharmacology)
• Electromyography
• Enterochromaffin Cells (drug effects, metabolism)
• Female
• Hydroxyindoleacetic Acid (metabolism)
• Hypersensitivity (drug therapy, metabolism, physiopathology, psychology)
• Male
• Maternal Deprivation
• Pain (drug therapy, metabolism, physiopathology, psychology)
• Pain Measurement
• Pain Threshold (drug effects)
• Pressure
• Rats
• Rats, Sprague-Dawley
• Serotonin (metabolism)
• Serotonin Plasma Membrane Transport Proteins (metabolism)
• Signal Transduction (drug effects)
• Time Factors