Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

Author:

Calixto-Campos Cassia1,Corrêa Mab P.1,Carvalho Thacyana T.1,Zarpelon Ana C.1,Hohmann Miriam S. N.1,Rossaneis Ana C.1,Coelho-Silva Leticia1,Pavanelli Wander R.1,Pinge-Filho Phileno1,Crespigio Jefferson1ORCID,Bernardy Catia C. F.2,Casagrande Rubia3ORCID,Verri Waldiceu A.1

Affiliation:

1. Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil

2. Department of Nursing, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil

3. Department of Pharmaceutical Sciences, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil

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-1βand TNFαand 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.

Publisher

Hindawi Limited

Subject

Cancer Research,Cell Biology,Molecular Medicine,General Medicine,Pathology and Forensic Medicine

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