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Evidence-Based Complementary and Alternative Medicine
Volume 2011, Article ID 452153, 11 pages
http://dx.doi.org/10.1093/ecam/neq018
Original Article

Biphasic Effect of Curcumin on Morphine Tolerance: A Preliminary Evidence from Cytokine/Chemokine Protein Array Analysis

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan
2Department of Anesthesiology, Taipei Medical University Hospital, Taipei Medical University, Taiwan
3Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
4Department of Anesthesiology, Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei Medical University, Taiwan
5Cancer Center, Wan-Fang Hospital, Taipei Medical University, Taiwan
6Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
7Pritzker School of Medicine, University of Chicago, IL, USA
8Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan

Received 22 June 2009; Accepted 8 February 2010

Copyright © 2011 Jui-An Lin 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 aim of this study was to evaluate the effect of curcumin on morphine tolerance and the corresponding cytokine/chemokine changes. Male ICR mice were made tolerant to morphine by daily subcutaneous injection for 7 days. Intraperitoneal injections of vehicle, low-dose or high-dose curcumin were administered 15 min after morphine injection, either acutely or chronically for 7 days to test the effect of curcumin on morphine-induced antinociception and development of morphine tolerance. On day 8, cumulative dose-response curves were generated and the 50% of maximal analgesic dose values were calculated and compared among groups. Corresponding set of mice were used for analyzing the cytokine responses by antibody-based cytokine protein array. Acute, high-dose curcumin enhanced morphine-induced antinociception. While morphine tolerance was attenuated by administration of low-dose curcumin following morphine injections for 7 days, it was aggravated by chronic high-dose curcumin following morphine injection, suggesting a biphasic effect of curcumin on morphine-induced tolerance. Of the 96 cytokine/chemokines analyzed by mouse cytokine protein array, 14 cytokines exhibited significant changes after the different 7-day treatments. Mechanisms for the modulatory effects of low-dose and high-dose curcumin on morphine tolerance were discussed. Even though curcumin itself is a neuroprotectant and low doses of the compound serve to attenuate morphine tolerance, high-doses of curcumin might cause neurotoxicity and aggravate morphine tolerance by inhibiting the expression of antiapoptotic cytokines and neuroprotective factors. Our results indicate that the effect of curcumin on morphine tolerance may be biphasic, and therefore curcumin should be used cautiously.