Therapeutic potential of tramadol and dextromethorphan on vincristine induced peripheral neuropathy in rats

Abstract

Vincristine is prescribed in many neoplastic diseases such as acute lymphoblastic leukaemia, Hodgkin's disease, non-Hodgkin's lymphomas, breast cancer, small cell lung cancer, cervical cancer, multiple myeloma. The neurotoxicity of vincristine is severe, being a dose limiting factor that depends on the cumulative dose and the frequency of administration. Data from clinical and preclinical studies show therapeutic potential for atypical opioid analgesics in neuropathic pain. In this research we investigated the analgesic potential for tramadol and dextromethorphan in animal model of vincristine-induced peripheral neuropathy. The peripheral neuropathy was induced in male Wistar rats by the daily intraperitoneal (i.p.) administration of vincristine sulphate 0.1 mg/kg/day, 5 days followed by 2 days break and then another 5 days of vincristine. Analgesics were given daily seven days after the vincristine treatment in the following doses: tramadol 5 mg/kg bw, dextromethorphan 20 mg/kg bw. We tracked the evolution of allodynia and mechanical hyperalgesia under analgesic treatment. Following the processing of experimental data, the first dose of tramadol significantly increased maximum response time, both in the assessment of allodynia and hyperalgesia. A single dose of dextromethorphan produced a significant inhibition of allodynia induced by vincristine (increases the time to response for paw retraction with 32.65 %, p < 0.001, vs vincristine group). Tramadol lead to the maximum anti-allodynic effect, immediately after the discontinuation of vincristine (141.73%, p < 0.001). Tramadol showed therapeutic potential in combating neuropathic pain induced by the administration of Vinca alkaloids.