Caffeic Acid Phenethyl Ester (CAPE) Attenuates Paclitaxel-induced Peripheral Neuropathy: A Mechanistic Study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a debilitating pain syndrome produced as a side effect of antineoplastic drugs like paclitaxel. Despite efforts, the currently available therapeutics suffer from serious drawbacks like unwanted side effects and poor efficacy and provide only symptomatic relief. Hence, there is a need to find new therapeutic alternatives for the treatment of chemotherapy-induced peripheral neuropathy. OBJECTIVE: The objective of this study was to explore the protective potential of caffeic acid phenethyl ester in paclitaxel-induced neuropathic pain. METHODS: We examined the effects of caffeic acid phenethyl ester by administering paclitaxel (2 mg/kg, intraperitoneal) to female Sprague Dawley rats on four alternate days to induce neuropathic pain, followed by the administration of caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneally). RESULTS: Rats that were administered paclitaxel showed a substantially diminished pain threshold and nerve functions after 28 days. A significantly increased protein expression of Wnt signalling protein (ß-catenin), inflammatory marker (matrix metalloproteinase 2) and a decrease in endogenous antioxidant (nuclear factor erythroid 2-related factor 2) levels were found in paclitaxel administered rats in comparison to the naïve control group. Caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneal) showed improvements in behavioural and nerve function parameters along with reduced expression of ß-catenin, matrix metalloproteinase 2 and an increase in nuclear factor erythroid 2- related factor 2 protein expression. CONCLUSION: The present study suggests that caffeic acid phenethyl ester attenuates chemotherapyinduced peripheral neuropathy via inhibition of ß-catenin and matrix metalloproteinase 2 and increases nuclear factor erythroid 2-related factor 2 activation.