CONICET | Buscador de Institutos y Recursos Humanos

Chemotherapy-induced peripheral neuropathy is a disabling conditioninduced by several frequently used chemotherapeutic drugs including the front-line agentoxaliplatin (OXA). Symptoms are predominantly sensory with the development ofneuropathic pain. Alternative dosing protocols and treatment discontinuation are the only availabletherapeutic strategies. The aim of our work was to evaluate the potential of a synthetic derivative of progesterone,17α-hydroxyprogesterone caproate (HPGC), in the prevention and treatment ofOXA-evoked painful neuropathy. We also evaluated glial activation at the dorsal rootganglia (DRG) and spinal cord levels as a possible target mechanism underlying HPGC actions. Male ratswere injected with OXA and HPGC following a prophylactic (HPGCp) or therapeutic (HPGCt)scheme (starting either before or after chemotherapy). The development ofhypersensitivity and allodynic pain and the expression of neuronal and glial activation markers wereevaluated. When compared to control animals, those receiving OXA showed a significant decrease inpaw mechanical and thermal thresholds, with the development of allodynia. Animals treated withHPGCp showed patterns of response similar to those detected in control animals, while thosetreated with HPGCt showed a suppression of both hypersensitivities after HPGCadministration. We also observed a significant increase in the mRNA levels of activating transcriptionfactor 3, c-fos, glial fibrillary acidic protein, ionized calcium binding adaptor protein 1, IL-1β and TNFα in DRG and spinal cord of OXA-injected animals, and significantly lower levels in ratsreceiving OXA and HPGC. These results show that HPGC administration reduces neuronal and glialactivation markers and is able to both prevent and suppress OXA-induced allodynia, suggesting apromising therapeutic strategy