P2X7 and P2Y1 receptors in DRG mediate electroacupuncture to inhibit peripheral sensitization in rats with IBS visceral pain

Although multiple purinergic receptors mediate the analgesic effects of acupuncture, it remains unclear whether there is mutual interaction between purinergic receptors to jointly mediate the electroacupuncture inhibition of peripheral sensitization in visceral pain. Visceral hypersensitivity was induced by intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rat. The antinociception effect of electroacupuncture on visceral pain was evaluated by morphology, behaviors, neuroelectrophysiology and molecular biology techniques. After labeling the colon-related primary sensory neurons with neural retrograde tracer and employing neuropharmacology, neuroelectrophysiology, and molecular biotechnology, the mechanisms of P2X7R, P2Y(1)R, and P2X3R in colon-related dorsal root ganglion (DRG) neurons alleviating visceral hypersensitivity of irritable bowel syndrome (IBS) by electroacupuncture at Zusanli and Sanyinjiao acupoints.were elucidated from the perspective of peripheral sensitization. Electroacupuncture significantly inhibited TNBS-induced colonic hypersensitivity in rats with IBS, and Satellite Glial Cells (SGCs) in DRG were found to be involved in electroacupuncture-mediated regulation of the electrophysiological properties of neurons. P2X7R was found to play a pain-inducing role in IBS visceral hypersensitivity by affecting P2X3R, and electroacupuncture exerted an analgesic effect by inhibiting P2X7R activation. P2Y(1)R was found to play an analgesic role in the process of visceral pain, mediating electroacupuncture to relieve visceral hypersensitivity. P2Y(1)R relieved visceral pain by inhibiting P2X3R in neurons associated with nociception, with P2X7R identified as upstream of P2Y(1)R up-regulation by electroacupuncture. Our study suggests that the P2X7R -> P2Y(1)R -> P2X3R inhibitory pathway in DRG mediates the inhibition of peripheral sensitization by electroacupuncture in rats with IBS visceral hypersensitivity.