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P2X3 in primary afferent neurons mediates the relief of visceral hypersensitivity by electroacupuncture in an irritable bowel syndrome rat model

张方  Zhe Ma  Zhijun Weng  Min Zhao  Huangan Wu  HANDan Zheng  Luyi Wu  Yuan Lu  Chunhui Bao  Yanan Liu  Huirong Liu  
【摘要】:Objective: To reveal the neurobiological mechanism by which the P2 X3 receptor of colonic primary sensory neurons in the dorsal root ganglia(DRG) of the lumbosacral segment(L6-S2)is involved in the alleviation of visceral hypersensitivity by electroacupuncture(EA) at the HeMu points in an irritable bowel syndrome(IBS) rat model.Methods: The IBS chronic visceral pain model was established in clean-grade male Sprague-Dawley(SD) rats according to the method of AL-chaer et al.At the 6 th week, bilateral EA at the He-Mu points(2/100 Hz, 1 mA,30 min) was conducted for intervention.The acupoints included the abdominal Tianshu point(ST25) and the Shangjuxu point(ST37).We conducted behavioral studies, histopathology of the colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction(PCR) assays to observe the role of the P2 X3 receptor in the colon and related DRG in relieving visceral hypersensitivity by EA.Results: 1) EA at the He-Mu points significantly reduced the visceral pain behavior scores of the IBS rats under different levels(20,40, 60, 80 mmHg) of colorectal distention(CRD) stimulation.2) EA downregulated the expression levels of the P2 X3 protein and its messenger RNA(mRNA) in the colon and related DRG of the IBS rats.3) EA regulated the electrical properties of the membranes [the resting membrane potential(RMP), rheobase and action potential(AP)] of colon-associated DRG neurons in the IBS rats with visceral hypersensitivity.Conclusion: EA can regulate the excitatory properties of DRG neurons by regulating the abnormally elevated P2 X3 receptor protein and mRNA expression levels in the colon and related DRG of IBS rats with visceral pain.The regulation of P2 X3 may be the important neurobiological mechanism by which EA at the He-Mu points relieves visceral hypersensitivity in IBS rats.

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