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.