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Analytical Cellular Pathology
Volume 2015 (2015), Article ID 285708, 18 pages
http://dx.doi.org/10.1155/2015/285708
Research Article

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

1Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil
2Department of Nursing, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil
3Department of Pharmaceutical Sciences, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil

Received 29 April 2015; Revised 9 July 2015; Accepted 12 July 2015

Academic Editor: Francesco A. Mauri

Copyright © 2015 Cassia Calixto-Campos 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

Cancer pain directly affects the patient’s quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti-inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor-induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1β and TNFα and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation.