Electroacupuncture Relieves Visceral Hypersensitivity via Balancing PAR2 and PAR4 in the Descending Pain Modulatory System of Goats

Abstract

Electroacupuncture (EA) is an efficient treatment for visceral hypersensitivity (VH). However, the mechanism underlying VH remains obscure. This study aimed to examine the effect of EA at Housanli acupoint on PAR2 and PAR4 expression in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cord dorsal horn (SCDH) axes, as well as on expression of the proinflammatory cytokines IL-1β and TNF-α, COX-2 enzyme, c-Fos, and the neuropeptides CGRP and SP in the same areas of the descending pain modulatory system. To induce VH in male goats, a 2,4,6-trinitrobenzene-sulfonic acid (TNBS)–ethanol solution was administered to the ileal wall. The visceromotor response (VMR) and nociceptive response at different colorectal distension pressures were measured to evaluate VH. Goats in the TNBS group displayed significantly increased VMR and nociceptive response scores, and elevated protein and mRNA levels of PAR2 and PAR4 in the descending pain modulatory system compared to those in the control group. EA alleviated VMR and nociceptive responses, decreased the protein and mRNA expression levels of PAR2, and elevated those of PAR4 in the descending pain modulatory system. EA may relieve VH by reducing PAR2 expression and increasing PAR4 expression in the descending pain modulatory system.

Paraventricular Mast Cell-Derived Histamine Activates CRH Neurons to Mediate Adult Visceral Hypersensitivity Induced by Neonatal Maternal Separation

“…Neuroinflammation in the CNS has been identified as the primary factor contrib to chronic pain [33,34]. Mast cells, being components of the innate immune system, r sent the "first responders" to various stress conditions rather than microglia [35].…”

“…Previous studies have highlighted the significance of mast cell-neuron interacti the development of chronic pain, encompassing visceral pain [37,38]. In the mamm Neuroinflammation in the CNS has been identified as the primary factor contributing to chronic pain [33,34]. Mast cells, being components of the innate immune system, represent the "first responders" to various stress conditions rather than microglia [35].…”