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The Scientific World Journal
Volume 2013 (2013), Article ID 240508, 8 pages
http://dx.doi.org/10.1155/2013/240508
Research Article

The Anticonvulsant Enaminone E139 Attenuates Paclitaxel-Induced Neuropathic Pain in Rodents

1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait
2Department of Pharmaceutical Sciences, School of Pharmacy, University of Saint Joseph, Hartford, CT 06103, USA

Received 22 October 2013; Accepted 20 November 2013

Academic Editors: S. Caccia and T. Nagai

Copyright © 2013 Dhandapani Thangamani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The enaminone methyl 4-(4′-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139) has anticonvulsant activities. It has been reported to have a better safety profile than some anticonvulsant drugs. Since some anticonvulsant drugs are used in the management of neuropathic pain, we evaluated the effects of E139 in rodent models of acute pain and paclitaxel-induced neuropathic pain. The reaction latency to thermal stimuli (hot-plate test) of BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel (2 mg/kg, i.p. for 5 consecutive days), and after treatment with E139 (0.1–40 mg/kg), amitriptyline (10 mg/kg), and gabapentin (10 and 30 mg/kg). Mechanical allodynia in paclitaxel-treated Sprague Dawley (SD) rats was measured using a dynamic plantar aesthesiometer before and after treatment with E139 (10 and 20 mg/kg) or its vehicle for four consecutive days from day 7 after first administration of paclitaxel (16 mg/kg on two alternate days). Administration of E139 (10–40 mg/kg) produced antinociceptive activity against thermal nociception in naïve mice. Treatment with E139, amitriptyline, or gabapentin reduced paclitaxel-induced thermal hyperalgesia. E139 reduced paclitaxel-induced mechanical allodynia, with the effects lasting longer (24 h) after repetitive dosing. Our results indicate that E139 has antinociceptive activity and attenuates paclitaxel-induced neuropathic pain in rodents.