Electroacupuncture alleviates capsaicin-induced rectal visceral pain in rats via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway

Electroacupuncture (EA), as a combination of traditional acupuncture and modern electrotherapy, and has analgesic effects on various acute and chronic pain. It has been proved to ameliorate chronic visceral pain, but its specific role in rectal visceral pain remains underexplored. A capsaicin (CAP)-induced visceral pain rat model was established, and behavioral pain responses were observed and recorded. Measurement of mechanical pain threshold was performed using electronic Von Frey system. Rectal tissues, and the activity of microglia cells were detected by Hematoxylin/eosin staining and immunofluorescence, respectively. Contents of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. Western blot was performed to determine the expressions of P2X4 Receptor (P2X4R), p38 mitogen-activated protein kinase (p38), phosphorylated p38 (p-p38), transient receptor potential vanilloid-1 (TRPV1) and ionized calcium binding adapter molecule 1 (Iba-1). Transfection efficiency of TRPV1 overexpression plasmids was examined by quantitative real-time polymerase chain reaction. EA abrogated CAP-induced upregulation of behavioral pain responses and mechanical threshold, damage on rectal tissue, activation of microglia, stimulation of inflammatory response and promotion of P2X4R-p38-TRPV1 pathway expressions in rats, while P2X4R activation reversed the effect of EA. P2X4R antagonist weakened CAP-induced upregulation of P2X4R-p38-TRPV1 pathway expressions, microglia activation as well as increase of IL-1β in HMO6 cells, which was reversed by TRPV1 overexpression. Collectively, EA improves CAP-induced rectal visceral pain via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway in microglia. However, the specificity role of P2X4R needs to be confirmed by more experiment.

Disease; Electroacupuncture; P2X4 receptor; P38 mitogen-activated protein kinase; Rectal visceral pain; Transient receptor potential vanilloid-1.