THERAPEUTIC POTENTIAL OF TRAMADOL AND
DEXTROMETHORPHAN ON VINCRISTINE INDUCED PERIPHERAL
NEUROPATHY IN RATS
CRISTINA ELENA ZBÂRCEA 1#, CORNEL CHIRIŢĂ 1#, EMIL ȘTEFĂNESCU 1#, OANA CRISTINA ȘEREMET 1#*, BRUNO ȘTEFAN VELESCU 1#, CRISTINA DANIELA MARINECI 1#, OVIDIU MUȘAT 2#, CARMEN GIUGLEA 3#, SIMONA NEGREŞ 1#
1Pharmacology and Clinical Pharmacy Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol
Davila”, 6 Traian Vuia Street, 020956, Bucharest, Romania
2Central Military Emergency Hospital, 139 Calea Plevnei Street, 010825 Bucharest, Romania
3“Sf. Ioan” Clinical Emergency Hospital, 13 Vitan Bârzești Road, 042122, Bucharest, Romania
*corresponding author: oana. seremet@yahoo.com
#Authors with equal contribution
Download Full Article

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.

Top