Effects of anti-rVEGF on the expression of VEGF receptor-2 and P2X2/3 receptors of the spinal dorsal horn in neuropathic pain rats

Neuropathic pain is caused by the peripheral or central nervous system structure damage or dysfunction. VEGF is involved in nociception and inflammation. VEGF may target VEGF receptor-2 (VEGFR-2) on the surface of neurons. P2X2/3 receptors play a crucial role in facilitating pain transmission at the spinal sites. Chronic constriction injury (CCI) rats were used as neuropathic pain model. Sprague-Dawley male rats were randomly divided into sham group, anti-recombinant VEGF antibody group with phosphate-buffer saline (anti-rVEGF + PBS group), CCI rats treated with phosphate-buffer saline group (CCI + PBS group) and CCI rats treated with anti-recombinant VEGF antibody group (CCI + anti-rVEGF group). The expressions of VEGFR-2, P2X2 and P2X3 protein in spinal dorsal horn (SDH) were detected by immunohistochemistry, double-label immunofluorescence and western blotting. The protein levels of VEGFR-2, P2X2 and P2X3 in L4/5 SDH of CCI + PBS group were higher than those in sham group. VEGFR-2 and P2X2 or P2X3 receptors were co-expressed in the cytoplasm and surface membranes of SDH. Anti-rVEGF treatment in CCI rats reduced the expression of VEGFR-2 and P2X2/3 receptors in L4/5 SDH compared with those in CCI + PBS group. Therefore, VEGF may activate VEGFR-2 to participate the process of neuropathic pain. Anti-rVEGF treatment in CCI rats reduced the expression of VEGFR-2 and inhibited the transmission of neuropathic pain in L4/5 SDH via decreasing the expression of P2X2/3. There is a cross-potentiation between VEGFR-2 and P2X2/3 receptors in neuropathic pain state.

► VEGF activate VEGFR-2 to participate the process of neuropathic pain.
► Anti-rVEGF treatment decreased the expression VEGFR-2 and P2X2/3.
► A cross-potentiation between VEGFR-2 and P2X2/3 in neuropathic pain state.