Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that is involved in the development of neuropathic pain. P2X7 receptor (P2X7) belongs to a class of ATP-gated nonselective cation channels that plays an important role in neuropathic pain. Nevertheless, little is known about the interaction between them for neuropathic pain. In this paper, we investigated role of TRPV4-P2X7 pathway in neuropathic pain. We evaluated the effect of TRPV4-P2X7 pathway on neuropathic pain in a chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) model. We analyzed the effect of P2X7 on mechanical and thermal hyperalgesia mediated by TRPV4 in CCD. Furthermore, we assessed the effect of TRPV4 on the expression of P2X7 and the release of IL-1β and IL-6 in DRG after CCD. We found that intraperitoneal injection of TRPV4 agonist GSK-1016790A led to a significant increase of mechanical and thermal hyperalgesia in CCD, which was partially suppressed by P2X7 blockade with antagonist Brilliant Blue G (BBG). Then, we further noticed that GSK-1016790A injection increased the P2X7 expression of CCD, which was decreased by TRPV4 blockade with antagonist RN-1734 and HC-067047. Furthermore, we also discovered that the expressions of IL-1β and IL-6 were upregulated by GSK-1016790A injection but reduced by RN-1734 and HC-067047. Our results provide evidence that P2X7 contributes to development of neuropathic pain mediated by TRPV4 in the CCD model, which may be the basis for treatment of neuropathic pain relief.