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TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism.
Pflugers Arch. 2012 Apr; 463(4):561-9.PA

Abstract

Paclitaxel produces a sensory neuropathy, characterized by mechanical and cold hypersensitivity, which are abated by antioxidants. The transient receptor potential vanilloid 4 (TRPV4) channel has been reported to contribute to paclitaxel-evoked allodynia in rodents. We recently showed that TRP ankyrin 1 (TRPA1) channel mediates oxaliplatin-evoked cold and mechanical allodynia, and the drug targets TRPA1 via generation of oxidative stress. Here, we have explored whether TRPA1 activation contributes to paclitaxel-induced mechanical and cold hypersensitivity and whether this activation is mediated by oxidative stress generation. Paclitaxel-evoked mechanical allodynia was reduced partially by the TRPA1 antagonist, HC-030031, and the TRPV4 antagonist, HC-067047, and was completely abated by the combination of the two antagonists. The reduced paclitaxel-evoked mechanical allodynia, observed in TRPA1-deficient mice, was completely abolished when mice were treated with HC-067047. Cold allodynia was abated completely by HC-030031 and in TRPA1-deficient mice. Exposure to paclitaxel of slices of mouse esophagus released the sensory neuropeptide, calcitonin gene-related peptide (CGRP). This effect was abolished by capsaicin desensitization and in calcium-free medium (indicating neurosecretion from sensory nerve terminals), partially reduced by either HC-030031 or HC-067047, and completely abated in the presence of glutathione (GSH). Finally, the reduced CGRP release, observed in esophageal slices of TRPA1-deficient mice, was further inhibited by GSH. Paclitaxel via oxygen radical formation targets TRPA1 and TRPV4, and both channels are key for the delayed development of mechanical allodynia. Cold allodynia is, however, entirely dependent on TRPA1.

Authors+Show Affiliations

Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, Florence, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22258694

Citation

Materazzi, Serena, et al. "TRPA1 and TRPV4 Mediate Paclitaxel-induced Peripheral Neuropathy in Mice Via a Glutathione-sensitive Mechanism." Pflugers Archiv : European Journal of Physiology, vol. 463, no. 4, 2012, pp. 561-9.
Materazzi S, Fusi C, Benemei S, et al. TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch. 2012;463(4):561-9.
Materazzi, S., Fusi, C., Benemei, S., Pedretti, P., Patacchini, R., Nilius, B., Prenen, J., Creminon, C., Geppetti, P., & Nassini, R. (2012). TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Archiv : European Journal of Physiology, 463(4), 561-9. https://doi.org/10.1007/s00424-011-1071-x
Materazzi S, et al. TRPA1 and TRPV4 Mediate Paclitaxel-induced Peripheral Neuropathy in Mice Via a Glutathione-sensitive Mechanism. Pflugers Arch. 2012;463(4):561-9. PubMed PMID: 22258694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. AU - Materazzi,Serena, AU - Fusi,Camilla, AU - Benemei,Silvia, AU - Pedretti,Pamela, AU - Patacchini,Riccardo, AU - Nilius,Bernd, AU - Prenen,Jean, AU - Creminon,Christophe, AU - Geppetti,Pierangelo, AU - Nassini,Romina, Y1 - 2012/01/19/ PY - 2011/12/20/received PY - 2011/12/28/accepted PY - 2012/1/20/entrez PY - 2012/1/20/pubmed PY - 2012/7/10/medline SP - 561 EP - 9 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 463 IS - 4 N2 - Paclitaxel produces a sensory neuropathy, characterized by mechanical and cold hypersensitivity, which are abated by antioxidants. The transient receptor potential vanilloid 4 (TRPV4) channel has been reported to contribute to paclitaxel-evoked allodynia in rodents. We recently showed that TRP ankyrin 1 (TRPA1) channel mediates oxaliplatin-evoked cold and mechanical allodynia, and the drug targets TRPA1 via generation of oxidative stress. Here, we have explored whether TRPA1 activation contributes to paclitaxel-induced mechanical and cold hypersensitivity and whether this activation is mediated by oxidative stress generation. Paclitaxel-evoked mechanical allodynia was reduced partially by the TRPA1 antagonist, HC-030031, and the TRPV4 antagonist, HC-067047, and was completely abated by the combination of the two antagonists. The reduced paclitaxel-evoked mechanical allodynia, observed in TRPA1-deficient mice, was completely abolished when mice were treated with HC-067047. Cold allodynia was abated completely by HC-030031 and in TRPA1-deficient mice. Exposure to paclitaxel of slices of mouse esophagus released the sensory neuropeptide, calcitonin gene-related peptide (CGRP). This effect was abolished by capsaicin desensitization and in calcium-free medium (indicating neurosecretion from sensory nerve terminals), partially reduced by either HC-030031 or HC-067047, and completely abated in the presence of glutathione (GSH). Finally, the reduced CGRP release, observed in esophageal slices of TRPA1-deficient mice, was further inhibited by GSH. Paclitaxel via oxygen radical formation targets TRPA1 and TRPV4, and both channels are key for the delayed development of mechanical allodynia. Cold allodynia is, however, entirely dependent on TRPA1. SN - 1432-2013 UR - https://www.unboundmedicine.com/medline/citation/22258694/TRPA1_and_TRPV4_mediate_paclitaxel_induced_peripheral_neuropathy_in_mice_via_a_glutathione_sensitive_mechanism_ L2 - https://dx.doi.org/10.1007/s00424-011-1071-x DB - PRIME DP - Unbound Medicine ER -