Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.

Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.
Exp Neurol. 2015 Nov 3;
Authors: Jiang SP, Zhang ZD, Kang LM, Wang QH, Zhang L, Chen HP
Abstract
Oxaliplatin (OXA) is the common and extremely potent anti-advanced colorectal cancer chemotherapeutic. Accumulating evidence reveals that OXA evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome and dose-limiting adverse effects is poorly understood. It is well known that cyclooxygenase-2 (COX-2) as well as phosphoinositide 3-kinase (PI3K)/Akt signaling mediate the neuropathic pain. But it is still unclear whether COX-2 or PI3K/Akt signaling participates in the regulation of OXA-induced hypersensitivity, as well as the linkage between COX-2 and PI3K/Akt signaling in mediating OXA-induced hypersensitivity. In this paper, we investigated the anti-nociceptive effect of celecoxib, an inhibitor of COX-2, on the OXA-induced neuropathic pain. We found that OXA increased the expression of cyclooxygenase-2 (COX-2) and Akt2 in the lumbar 4-5 (L4-5) dorsal root ganglion (DRG). And the administration of celecoxib alleviates the OXA-induced hypersensitivity and suppresses the COX-2 and PI3K/Akt2 signaling. Our findings showed that COX-2 and PI3K/Akt2 signaling in DRG contributed to the OXA-induced neuropathic pain. In addition, celecoxib enhanced the OXA-induced mortality of the human...

Source: Experimental Neurology - November 3, 2015 Category: Neurology Authors: Jiang SP, Zhang ZD, Kang LM, Wang QH, Zhang L, Chen HP Tags: Exp Neurol Source Type: research