• Caren Tatiane De David Antoniazzi, Romina Nassini, Flávia Karine Rigo, Alessandra Marcon Milioli, Fernando Bellinaso, Camila Camponogara, Cássia Regina Silva, Amanda Spring de Almeida, Mateus Fortes Rossato, Francesco De Logu, Sara Marchesan Oliveira, Thiago Mattar Cunha, Pierangelo Geppetti, Juliano Ferreira, and Gabriela Trevisan.
• Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil.
• Int. J. Cancer. 2019 Jan 15; 144 (2): 355-365.

AbstractThere 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, α-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.© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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