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Pharmacol Res ; 152: 104576, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790822

RESUMO

Breast carcinoma causes severe pain, which decreases the quality of life of patients. Current treatments produce adverse effects and have limited efficacy. Transient potential receptor ankyrin 1 (TRPA1) is related to the onset of cancer and neuropathic pain. The aim of this study was to evaluate the involvement of TRPA1 in a model of breast carcinoma. We injected 4T1 cells in the fourth caudal mammary fat pad of female BALB/c mice, and after 20 days we observed mechanical and cold allodynia and spontaneous nociception behavior (mouse grimace scale detection, MGS). TRPA1 selective antagonist (HC-030031 or A-967079) administration or intrathecal administration of TRPA1 antisense (AS) oligonucleotide was performed. The activity of NADPH oxidase, superoxide dismutase (SOD) and hydrogen peroxide (H2O2) levels were evaluated. The chemical hyperalgesia produced by a TRPA1 agonist (allyl isothiocyanate, AITC) was also detected. The administration of TRPA1 antagonists, TRPA1 AS, or antioxidant, transiently attenuated MGS, or mechanical and cold allodynia. Intraplantar injection of AITC also caused nociception. NADPH oxidase or SOD activity and H2O2 levels were increased in the sciatic nerve and hind paw skin samples. The 4T1 cells did not express TRPA1, and the use of HC-030031 or α-lipoic acid did not reduce the cytotoxic effect of a chemotherapeutic drug (paclitaxel). Thus, TRPA1 could be investigated as a target for breast carcinoma pain treatment.


Assuntos
Dor do Câncer , Neoplasias Mamárias Experimentais , Canal de Cátion TRPA1 , Acetanilidas/farmacologia , Acetanilidas/uso terapêutico , Analgésicos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Dor do Câncer/tratamento farmacológico , Dor do Câncer/etiologia , Dor do Câncer/genética , Dor do Câncer/metabolismo , Linhagem Celular Tumoral , Feminino , Peróxido de Hidrogênio/metabolismo , Hiperalgesia/tratamento farmacológico , Neoplasias Mamárias Experimentais/complicações , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Camundongos Endogâmicos BALB C , NADPH Oxidases/metabolismo , Nociceptividade/efeitos dos fármacos , Oximas/uso terapêutico , Paclitaxel/farmacologia , Purinas/farmacologia , Purinas/uso terapêutico , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Pele/metabolismo , Superóxido Dismutase/metabolismo , Canal de Cátion TRPA1/antagonistas & inibidores , Canal de Cátion TRPA1/genética , Ácido Tióctico/uso terapêutico
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