Oxaliplatin evokes P2X7-dependent glutamate release in the cerebral cortex: A pain mechanism mediated by Pannexin 1.

摘要: Abstract Anticancer therapy based on the repeated administration of oxaliplatin is limited by development a neuropathic syndrome difficult to treat. Oxaliplatin neurotoxicity complex nervous mechanisms, comprehension role single neurotransmitters and knowledge signal flow among cells matter importance improve therapeutic chances. In rat model oxaliplatin-induced neuropathy, we report increased P2X7-evoked glutamate release from cerebrocortical synaptosomes. The was abolished P2X7 receptor (P2X7R) antagonists Brilliant-Blue-G (BBG) A-438079, significantly reduced Carbenoxolone Pannexin 1 (Panx1) selective inhibitors Erioglaucine 10 Panx suggesting recruitment Panx1. Aimed evaluate significance P2X7R-Panx1 system activation in pain generated oxaliplatin, pharmacological modulators were spinally infused intrathecal catheter oxaliplatin-treated animals. BBG, reverted oxaliplatin-dependent pain. Finally, influence blockade anticancer activity evaluated human colon cancer cell line HT-29. Prevention HT-29 apoptosis mortality dependent kind concentration P2X7R antagonists. On contrary, inhibition Panx1 did not alter lethality tumor cells. It concluded that nerve terminals rats; increase mediated functional Panx1; revert pain; do channel suggested as new safe target.