Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice.

The aim of this study was to evaluate the participation of the endothelin ET_A and ET_B receptors and the effects of bosentan in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice. Adult male Swiss mice received 1 mg/kg of oxaliplatin intravenously, twice a week for 5 weeks. Dorsal root ganglia (DRG) and spinal cords were removed for evaluation of the endothelin ET_A and ET_B receptor expression. Afterwards, selective (BQ-123 and BQ-788; 10 nmol in 30 μL, intraplantarly) and non-selective (bosentan, 100 mg/kg, orally) antagonists were administered in order to evaluate the involvement of the endothelin receptors in OIN. Mechanical and thermal nociception tests were performed once a week for 56 days. Oxaliplatin induced mechanical and thermal hypersensitivity and increased the endothelin ET_A receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ET_B receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ET_A and ET_B receptor selective antagonists partially prevented mechanical hyperalgesia in mice with OIN (P < 0.05). Moreover, bosentan prevented mechanical and thermal hypersensitivity in oxaliplatin-treated mice (P < 0.05). In conclusion, both endothelin ET_A and ET_B receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.

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