It has been demonstrated that P2X receptors family is involved in nociceptors sensitization. Two of them, P2X4 and P2X7 receptors (P2X4R-P2X7R), play a major role in different models of hyperalgesia. Recently, we demonstrated that P2X4 in the dorsal root ganglion (DRG) is essential to the development of streptozotocin-induced (diabetic) neuropathic hyperalgesia. The aim of this study was to investigate whether P2X4R or P2X7R in DRG are involved in the development and maintenance of paclitaxel-induced early and late mechanical hyperalgesia. Neuropathic hyperalgesia was induced with 1 (early) or 4 (late) administrations of paclitaxel (1 mg / kg, intraperitoneal), and the selective antagonist of P2X4R (PSB 12062, 1 mmol / 5 µL) or P2X7R (A- 740003, 0.1 mmol / 5µL) was injected in DRG (L5) 3h after the administration of the initial dose of paclitaxel, or on 13th day after induction. Mechanical hyperalgesia was measured using the electronic von Frey and DRG were harvested to verify the expression of P2X4R and P2X7R by immunogold technique. The results demonstrated that both P2X4R and P2X7R of DRG are involved in paclitaxel-induced early and late neuropathic hyperalgesia. The immunogold labeling revealed that P2X4R and P2X7R are detected in mitochondria, cytosol, and plasma membrane of both DRG satellite cells and neurons. These results suggest that the activation of P2X4R and P2X7R in DRG might be a key event during development and maintenance of paclitaxel-induced mechanical hyperalgesia and are promising targets for the paclitaxel-induced neuropathic pain control.

THE INVOLVEMENT OF P2X4 AND P2X7 PURINERGIC RECEPTORS OF DORSAL ROOT GANGLIA ON PACLITAXEL-INDUCED NEUROPATHIC PAIN