Quercetin reduces Ehrlich tumor-induced cancer pain in mice.

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.

• Authors: Cassia Calixto-Campos, Mab P Corrêa, Thacyana T Carvalho, Ana C Zarpelon, Miriam S N Hohmann, Ana C Rossaneis, Leticia Coelho-Silva, Wander R Pavanelli, Phileno Pinge-Filho, Jefferson Crespigio, Catia C F Bernardy, Rubia Casagrande, Waldiceu A Verri Jr
• Journal: Analytical cellular pathology (Amsterdam) (Anal Cell Pathol (Amst)) Vol. 2015 Pg. 285708 ( 2015) ISSN: 2210-7185 [Electronic] United States
• PMID: 26351625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Analgesics, Opioid
• Anti-Inflammatory Agents
• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• Naloxone
• Morphine
• Quercetin

Topics

• Analgesics (pharmacology, therapeutic use)
• Analgesics, Opioid (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Carcinoma, Ehrlich Tumor (complications)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Interleukin-1beta (biosynthesis)
• Male
• Mice
• Morphine (pharmacology, therapeutic use)
• Naloxone (pharmacology, therapeutic use)
• Neutrophil Infiltration (drug effects)
• Oxidative Stress
• Pain (drug therapy, etiology, pathology)
• Quercetin (pharmacology, therapeutic use)
• Skin (pathology)
• Spinal Cord (pathology)
• Tumor Necrosis Factor-alpha (biosynthesis)