PMID- 30289972 OWN - NLM STAT- MEDLINE DCOM- 20190405 LR - 20200225 IS - 1097-0215 (Electronic) IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 144 IP - 2 DP - 2019 Jan 15 TI - Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain. PG - 355-365 LID - 10.1002/ijc.31911 [doi] AB - There is a major, unmet need for the treatment of cancer pain, and new targets and medicines are required. The transient receptor potential ankyrin 1 (TRPA1), a cation channel expressed by nociceptors, is activated by oxidizing substances to mediate pain-like responses in models of inflammatory and neuropathic pain. As cancer is known to increase oxidative stress, the role of TRPA1 was evaluated in a mouse model of cancer pain. Fourteen days after injection of B16-F10 murine melanoma cells into the plantar region of the right hind paw, C57BL/6 mice exhibited mechanical and thermal allodynia and thigmotaxis behavior. While heat allodynia was partially reduced in TRP vanilloid 1 (TRPV1)-deficient mice, thigmotaxis behavior and mechanical and cold allodynia were absent in TRPA1-deficient mice. Deletion of TRPA1 or TRPV1 did not affect cancer growth. Intrathecal TRPA1 antisense oligonucleotides and two different TRPA1 antagonists (HC-030031 or A967079) transiently attenuated thigmotaxis behavior and mechanical and cold allodynia. A TRPV1 antagonist (capsazepine) attenuated solely heat allodynia. NADPH oxidase activity and hydrogen peroxide levels were increased in hind paw skin 14 days after cancer cell inoculation. The antioxidant, alpha-lipoic acid, attenuated mechanical and cold allodynia and thigmotaxis behavior, but not heat allodynia. Whereas TRPV1, via an oxidative stress-independent pathway, contributes partially to heat hypersensitivity, oxidative stress-dependent activation of TRPA1 plays a key role in mediating thigmotaxis behavior and mechanical and cold allodynia in a cancer pain model. TRPA1 antagonists might be beneficial in the treatment of cancer pain. CI - (c) 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. FAU - Antoniazzi, Caren Tatiane De David AU - Antoniazzi CTD AD - Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. FAU - Nassini, Romina AU - Nassini R AD - Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy. FAU - Rigo, Flavia Karine AU - Rigo FK AD - Graduate Program in Health Science, University of the Extreme South of Santa Catarina, Unesc, Criciuma, Santa Catarina, Brazil. FAU - Milioli, Alessandra Marcon AU - Milioli AM AD - Graduate Program in Health Science, University of the Extreme South of Santa Catarina, Unesc, Criciuma, Santa Catarina, Brazil. FAU - Bellinaso, Fernando AU - Bellinaso F AD - Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. FAU - Camponogara, Camila AU - Camponogara C AD - Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. FAU - Silva, Cassia Regina AU - Silva CR AD - Biochemistry and genetics Institute, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil. AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - de Almeida, Amanda Spring AU - de Almeida AS AD - Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. FAU - Rossato, Mateus Fortes AU - Rossato MF AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - De Logu, Francesco AU - De Logu F AD - Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy. FAU - Oliveira, Sara Marchesan AU - Oliveira SM AD - Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. FAU - Cunha, Thiago Mattar AU - Cunha TM AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - Geppetti, Pierangelo AU - Geppetti P AD - Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy. FAU - Ferreira, Juliano AU - Ferreira J AD - Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), Florianopolis, Santa Catarina, Brazil. FAU - Trevisan, Gabriela AU - Trevisan G AUID- ORCID: 0000-0003-0137-5034 AD - Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil. AD - Graduate Program in Health Science, University of the Extreme South of Santa Catarina, Unesc, Criciuma, Santa Catarina, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181030 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (TRPA1 Cation Channel) RN - 0 (Trpa1 protein, mouse) SB - IM MH - Animals MH - Cancer Pain/*metabolism MH - Male MH - *Melanoma, Experimental MH - Mice MH - Mice, Inbred C57BL MH - TRPA1 Cation Channel/*metabolism PMC - PMC6587729 OTO - NOTNLM OT - HC-030031 OT - NADPH oxidase OT - allodynia OT - chemotherapeutic drugs OT - hydrogen peroxide EDAT- 2018/10/06 06:00 MHDA- 2019/04/06 06:00 PMCR- 2019/06/21 CRDT- 2018/10/06 06:00 PHST- 2018/05/20 00:00 [received] PHST- 2018/08/27 00:00 [revised] PHST- 2018/09/19 00:00 [accepted] PHST- 2018/10/06 06:00 [pubmed] PHST- 2019/04/06 06:00 [medline] PHST- 2018/10/06 06:00 [entrez] PHST- 2019/06/21 00:00 [pmc-release] AID - IJC31911 [pii] AID - 10.1002/ijc.31911 [doi] PST - ppublish SO - Int J Cancer. 2019 Jan 15;144(2):355-365. doi: 10.1002/ijc.31911. Epub 2018 Oct 30.