In Rats, the Chemotherapeutic Drug Vincristine-Induced Neuropathic Nociception is Suppressed When Cannabinoid CB1 and CB2 Receptors are Activated

Abstract

Rats were used to test the potential of cannabis to reduce mechanical hypersensitivity, or mechanical allodynia, which was brought on by vincristine chemotherapy. After that, action sites were located. Method of experimentation: After ten daily injections of vincristine, mechanical hypersensitivity developed in comparison to those that received saline at the same periods. The effects on chemotherapy-induced neuropathy were assessed for the CB1/CB2 receptor agonist WIN55, 212-2, the receptor-inactive enantiomer WIN55, 212-3, the CB2-selective agonist (R,S)-AM1241, the opiate agonist morphine, and vehicle. To determine the locations of action, WIN55, 212-2 was injected either locally in the hind paw or intrathecally (i.t.). By employing competitive antagonists for either CB1 (SR141716) or CB2 receptors (SR144528), pharmacological selectivity was demonstrated. Vincristine-evoked mechanical allodynia was decreased when WIN55, 212-2, but not WIN55, 212-3, were administered systemically. A change in the dose-response curve to the left was noticed after WIN55, 212-2 in comparison to morphine therapy. Antibodies of CB1 (SR141716) and CB2 (SR144528) inhibited WIN55, 212-2’s anti-allodynic actions. Via a CB2 mechanism, (R,S)-AM1241 reduced c-induced mechanical hypersensitivity. Without causing catalepsy, both cannabinoid agonists reduced the mechanical hypersensitivity brought on by vincristine. Cannabis-induced neuropathy may be modulated by cannabinoids at spinal sites of action. When delivered intraperitoneally, WIN55, 212-2 but not WIN55,212-3 inhibited vincristine-evoked mechanical hypersensitivity at dosages that were inert after local hindpaw injection. Spinal co-administration of CB1 and CB2 antagonists inhibited WIN55,212-2’s anti-allodynic effects.By activating CB1 and CB2 receptors, cannabinoids inhibit the maintenance of vincristine-induced mechanical allodynia. The spinal cord is involved in the mediation of these anti-allodynic actions, at least partially.