Attenuation of vincristine-induced neuropathy by synthetic cyclohexenone-functionalized derivative in mice model

Vincristine (VCR) is a well-known anticancer drug which frequently induced painful neuropathy and impairs the quality of life of patients. The present study was designed to investigate the alleviative potential of a novel cyclohexenone derivative (CHD), i.e., ethyl 6-(4-methoxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate, against VCR-induced neuropathic pain in mice model. VCR was administered intraperitoneally for 10 days in two cycles to induce neuropathic pain. Static and dynamic mechanical allodynia was evaluated using von Frey hair filaments and cotton buds, respectively. Paw thermal hyperalgesia was determined through a hot plate analgesiometer. The tail cold immersion hyperalgesia and paw cold allodynia were determined by available standard protocols. The formalin nociception was induced via subplantar injection of formalin. The antioxidant potential was evaluated via 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. The outcome of this study revealed that CHD (30-45 mg/kg) and gabapentin (75 mg/kg) significantly enhanced the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in static and dynamic allodynia, respectively, and increased the PWL in thermal hyperalgesia and tail withdrawal latency (TWL) as compared to the VCR-treated group. CHD significantly augmented the paw withdrawal duration (PWD) in paw cold allodynia, while the same compound only increased the paw elevation and paw licking in the delayed phase of formalin nociception. Moreover, CHD significantly inhibited the DPPH free radical scavenging action (IC50 = 56), butylated hydroxytoluene (BHT) (IC50 = 39), and ascorbic acid (IC50 = 2.93). In conclusion, CHD exhibited a profile of potential attenuative effect against the VCR-induced neuropathic pain which might be attributed to its possible antinociceptive and antioxidant effect.