Prophylactic Cannabinoid Administration Blocks the Development of Paclitaxel-Induced Neuropathic Nociception during Analgesic Treatment and following Cessation of Drug Delivery

• DOI: 10.1186/1744-8069-10-27
• Publication Date: 2014-04-18T05:39:09Z
• Authors: Elizabeth J Rahn; Liting Deng; Ganesh A Thakur; Kiran Vemuri; Alexander M Zvonok; Yvonne Y Lai; Alexandros Makriy...; Andrea G Hohmann
• Keywords: AM251; Allodynia

Chemotherapeutic treatment results in chronic pain an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics urgent one. We compared effects prophylactic cannabinoids as a preventative strategy suppressing development paclitaxel-induced nociception. The mixed CB1/CB2 agonist WIN55,212-2 was with cannabilactone CB2-selective AM1710, administered subcutaneously (s.c.), via osmotic mini pumps before, during, after paclitaxel treatment. Pharmacological specificity assessed using CB1 (AM251) CB2 (AM630) antagonists. impact drug infusion on transcriptional regulation mRNA markers astrocytes (GFAP), microglia (CD11b) cannabinoid receptors (CB1, CB2) lumbar spinal cords vehicle-treated rats.Both AM1710 blocked mechanical cold allodynia; anti-allodynic efficacy persisted approximately two to three weeks following cessation delivery. (0.1 0.5 mg/kg/day s.c.) suppressed both allodynia. WIN55,212-2-mediated suppression hypersensitivity dominated by activation whereas allodynia relatively insensitive blockade either (AM251; 3 or (AM630; (0.032 3.2 mg/kg /day) only highest dose (3.2 Anti-allodynic were mediated CB2. outlasted that produced infusion. expression levels astrocytic marker GFAP marginally increased microglial CD11b unchanged. Both (0.5 cord paclitaxel-treated rats manner AM630.Cannabinoids block neuropathy protect against neuropathic Chronic selective CB2-dependent fashion. Our support therapeutic potential chemotherapy-induced humans.