RESEARCH ARTICLE
Transient Receptor Potential Channels in Chemotherapy-Induced Neuropathy
Romina Nassini*, 1, Silvia Benemei1, Camilla Fusi1, Gabriela Trevisan1, 2, Serena Materazzi1
Article Information
Identifiers and Pagination:
Year: 2013Volume: 6
First Page: 127
Last Page: 136
Publisher ID: TOPAINJ-6-127
DOI: 10.2174/1876386301306010127
Article History:
Received Date: 09/08/2012Revision Received Date: 09/08/2012
Acceptance Date: 16/08/2012
Electronic publication date: 08/3/2013
Collection year: 2013
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side effect of many chemotherapeuticdrugs, including platinum-based compounds (e.g., cisplatin and oxaliplatin), taxanes (e.g., paclitaxel), vinca alkaloids (e.g., vincristine), and the first-in-class proteasome inhibitor, bortezomib. Among the various sensory symptoms of CIPN, paresthesia, dysesthesia, spontaneous pain, and mechanical and thermal hypersensitivity are prominent. Inflammation, oxidative stress, loss of intraepidermal nerve fibers, modifications of mitochondria, and various ion channels alterations are part of the several mechanisms contributing to CIPN. Because attempts to mitigate chemotherapeutic- induced acute neuronal hyperexcitability and the subsequent peripheral neuropathy have yielded unsatisfactory results, a more in-depth understanding of the mechanism(s) responsible for the neurotoxic action of anticancer drugs is required.
Some members of the transient receptor potential (TRP) family of channels, as the TRPV1 and TRPV4 (vanilloid), TRPA1 (ankyrin) and TRPM8 (melastatin) are expressed on the plasma membrane of primary sensory neurons (nociceptors), where they are activated by an unprecedented series of physical and chemical stimuli. There is evidence that TRPV1, TRPV4, TRPA1 and TRPM8 are prominent contributors of mechanical and thermal hypersensitivity in models of CIPN. In particular, in vitro and in vivo studies have pointed out the unique role of TRPA1 and oxidative stress in the mechanism responsible for cold and mechanical hyperalgesia in rodent models of CIPN.
