Caratterizzazione dell'effetto analgesico di un nuovo ligando del recettore I2 imidazolinico in un modello animale di dolore neuropatico indotto da bortezomib

Bortezomib (BTZ) is a proteasome inhibitor that shows potent antineoplastic effects mainly in the treatment of the multiple myeloma. However, BTZ induces a painful neuropathy that causes a significant impairment of patient’s quality of life. CR4056 is a novel imidazoline-2 (I2) ligand that acts modulating the levels of monoamino oxidase (MAO), and it is characterized by a relevant efficacy in several animal models of pain. This study was designed to test the efficacy of CR4056 in a chronic model of BTZ-induced neurotoxicity, compared with two well known analgesic, buprenorphine and gabapentin. Besides, the effect of CR4056 in preventive and therapeutic schedule was evaluated. After 8 weeks of treatment, BTZ reduced nerve conduction velocity (NCV) and induced allodynia. CR4056, gabapentin or buprenorphine in neuropathic animals did not reverse the impaired NCV. By contrast, the optimal CR4056 dose reversed BTZ-induced allodynia. This effect was persistent along the treatment period without rebound after suspension. These results promote the use of CR4056 as a potential treatment in the chronic neuropathic pain therapy.