Activation of cannabinoid CB1 and CB2 receptors suppresses painful peripheral neuropathy evoked by the chemotherapeutic agent vincristine
Rahn, Elizabeth Jocelyn
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Chemotherapeutic treatment with vincristine induces severe side-effects including neuropathic pain. The present study was conducted to evaluate the efficacy of cannabinoids in suppressing vincristine-induced behavioral sensitization to mechanical stimulation (tactile allodynia). WIN55,212-2 (0.75-2.5 mg/kg i.p.), a potent cannabinoid agonist, induced a dose-dependent suppression of mechanical hypersensitivity in vincristine-treated rats. By contrast, WIN55,212-3, the receptor inactive enantiomer of WIN55,212-2, did not alter mechanical withdrawal thresholds relative to vehicle. The CB1 antagonist SR141716 (2.5 mg/kg i.p.) and CB2 antagonist SR144528 (2.5 mg/kg i.p.) blocked the anti-allodynic effects of WIN55,212-2. The CB2 selective agonist AM1241 (2.5 mg/kg i.p.) also suppressed vincristine-induced mechanical hypersensitivity, and this effect was blocked by the CB2 but not the CB1 antagonist. By contrast, the opiate analgesic morphine (2.5 mg/kg i.p.), did not alter vincristine-induced mechanical hypersensitivity relative to control conditions. The present results provide evidence that cannabinoids suppress chemotherapy-evoked neuropathy through activation of both CB1 and CB2 receptors.