Anti-Nociceptive Synergism of Pregabalin and Xylopic acid Co-administration in Paclitaxel-induced Neuropathy: Isobolographic Analysis

Background: Paclitaxel-induced neuropathy still remains a clinical problem for patients undergoing chemotherapy. Objective: The objective of the study was to determine the interaction between xylopic acid and pregabalinco-administration as well as their toxicity in paclitaxel-induced neuropathy. Materials and Methods: Neuropathic pain was induced in rats with 2 mg/kg of paclitaxel on alternative days for four days (days 0, 2, 4 and 6). Equi effective doses of xylopic acid and pregabalin that produced 50% anti-nociception (ED50) were determined from their log-dose response curves in the cold allodynia and thermal pain tests. Xylopic acid and pregabalin were again administered to rats in a fixed ratio combination (1:1) of their ED50’sin order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to a theoretical ED50 (Zadd). Blood samples from the various treatment groups of rats were collected for toxicological assessment of the co-administered compounds. Results: The Zexplay below the Zadd on the isobologram of the cold allodnia test. The co-administration exhibited additivity in the thermal pain test. The co-administration did not produce significant (p>0.05) toxicity in rats. The co-administration may be beneficial in paclitaxel-induced neuropathy.

Key words: Isobolograms, Neuropathic pain, Paclitaxel, xylopic acid, Toxicity.