Role of transient receptor potential ankyrin 1 (TRPA1) on nociception caused by a murine model of breast carcinoma

Pharmacol Res. 2020 Feb:152:104576. doi: 10.1016/j.phrs.2019.104576. Epub 2019 Nov 29.

Abstract

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.

Keywords: A-967079 (PubChem CID: 98082461); Allodynia; Allyl Isothiocyanate (PubChem CID: 128851); HC-030031; HC-030031 (PubChem CID: 1150897); Hydrogen peroxide; NADPH oxidase; Paclitaxel; α-Lipoic Acid (PubChem CID: 6112); α-Lipoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Acetanilides / therapeutic use
  • Analgesics / therapeutic use
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cancer Pain* / drug therapy
  • Cancer Pain* / etiology
  • Cancer Pain* / genetics
  • Cancer Pain* / metabolism
  • Cell Line, Tumor
  • Female
  • Hydrogen Peroxide / metabolism
  • Hyperalgesia / drug therapy
  • Mammary Neoplasms, Experimental* / complications
  • Mammary Neoplasms, Experimental* / drug therapy
  • Mammary Neoplasms, Experimental* / genetics
  • Mammary Neoplasms, Experimental* / metabolism
  • Mice, Inbred BALB C
  • NADPH Oxidases / metabolism
  • Nociception / drug effects
  • Oximes / therapeutic use
  • Paclitaxel / pharmacology
  • Purines / pharmacology
  • Purines / therapeutic use
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Skin / metabolism
  • Superoxide Dismutase / metabolism
  • TRPA1 Cation Channel* / antagonists & inhibitors
  • TRPA1 Cation Channel* / genetics
  • Thioctic Acid / therapeutic use

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • A 967079
  • Acetanilides
  • Analgesics
  • Antineoplastic Agents, Phytogenic
  • Oximes
  • Purines
  • TRPA1 Cation Channel
  • Trpa1 protein, mouse
  • Thioctic Acid
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • NADPH Oxidases
  • Paclitaxel