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, 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.

Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain / Antoniazzi, Caren Tatiane De David; Nassini, Romina; Rigo, Flávia Karine; Milioli, Alessandra Marcon; Bellinaso, Fernando; Camponogara, Camila; Silva, Cássia Regina; de Almeida, Amanda Spring; Rossato, Mateus Fortes; De Logu, Francesco; Oliveira, Sara Marchesan; Cunha, Thiago Mattar; Geppetti, Pierangelo; Ferreira, Juliano; Trevisan, Gabriela. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - ELETTRONICO. - (2018), pp. 0-.. [10.1002/ijc.31911]

Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain

Nassini, Romina;De Logu, Francesco;Geppetti, Pierangelo;Ferreira, Juliano;Trevisan, Gabriela
2018

Abstract

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, 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
0
.
Goal 3: Good health and well-being for people
Antoniazzi, Caren Tatiane De David; Nassini, Romina; Rigo, Flávia Karine; Milioli, Alessandra Marcon; Bellinaso, Fernando; Camponogara, Camila; Silva, Cássia Regina; de Almeida, Amanda Spring; Rossato, Mateus Fortes; De Logu, Francesco; Oliveira, Sara Marchesan; Cunha, Thiago Mattar; Geppetti, Pierangelo; Ferreira, Juliano; Trevisan, Gabriela
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1138608
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