Electroacupuncture intervention of visceral hypersensitivity is involved in PAR-2-activation and CGRP-release in the spinal cord

Manoj K Shah,Yi Ding,Ming-Xing Ding,Vitaly Vodyanoy,Habibullah Janyaro,Adnan Hassan Tahir,Juan Wan

doi:10.1038/s41598-020-67702-2

Abstract

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T11) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBS-treated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7–22. Goats of Sham-A, VH or EA group showed higher (P < 0.01) VH at days 7–22 than the Control-goats. EA-treated goats exhibited lower (P < 0.01) VH as compared with Sham-A or VH group. Immunoreactive-cells and expression-levels of spinal PAR-2, CGRP and c-Fos in the EA group were greater (P < 0.01) than those in the Control group, but less (P < 0.01) than those in Sham-A and VH groups on day 22. Downregulation of spinal PAR-2 and CGRP levels by EA attenuates the ileitis and resultant VH.

Highlights

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases
The roles of calcitonin gene-related peptide (CGRP) in VH have been confirmed with CGRP-knockout and CGRP-receptor antagonists in r odents[19,20,21,22]. These findings demonstrate that spinal PAR-2 activation and the release of PAR-2-mediated CGRP contribute to the development of VH
As compared with Control group, the goats of VH, Sham acupuncture (Sham-A) and EA groups resulted in lower (P = 0.008, 0.045 and 0.049) body weight at 7 days [F (3, 32) = 5.380, P = 0.004]

Summary

Introduction

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. Fecal supernatant of the patients with irritable bowel syndrome into the colon of healthy mice resulted in higher intestinal permeability, mucosal inflammation and subsequent VH through a PAR-2 activation m echanism[12,13,14]. These studies clearly indicate that activated PAR-2 in the intestines facilitates VH. The roles of CGRP in VH have been confirmed with CGRP-knockout and CGRP-receptor antagonists in r odents[19,20,21,22] These findings demonstrate that spinal PAR-2 activation and the release of PAR-2-mediated CGRP contribute to the development of VH. Whether EA relieves ileitisinduced VH through suppressing the spinal PAR-2 activation or PAR-2-mediated CGRP release is not reported

Methods

Results

Conclusion