Quercetin reduces Ehrlich tumor-induced cancer pain in mice.
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.
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Cassia
C
Calixto-Campos
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Mab P
MP
Corrêa
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Thacyana T
TT
Carvalho
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Ana C
AC
Zarpelon
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Miriam S N
MS
Hohmann
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Ana C
AC
Rossaneis
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Leticia
L
Coelho-Silva
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Wander R
WR
Pavanelli
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Phileno
P
Pinge-Filho
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Jefferson
J
Crespigio
Department of Nursing, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil.
Catia C F
CC
Bernardy
Department of Pharmaceutical Sciences, Health Science Centre, Londrina State University, Avenue Robert Koch 60, 86038-350 Londrina, PR, Brazil.
Rubia
R
Casagrande
Department of Pathology, Biological Sciences Centre, Londrina State University, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, PR, Brazil.
Waldiceu A
WA
Verri
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000700:Analgesics; D000701:Analgesics, Opioid; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D009020:Morphine; D011794:Quercetin