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Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field.
Br J Pharmacol. 2018 06; 175(12):2185-2203.BJ

Abstract

Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of transient receptor potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 cation channels as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically. TRPV1 channel antagonists have suffered from side effects related to the channel's role in temperature sensation; however, high dose formulations of capsaicin have reached the market and shown therapeutic utility. A number of potent, small molecule antagonists of TRPA1 channels have recently advanced into clinical trials for the treatment of inflammatory and neuropathic pain, and TRPM8 antagonists are following closely behind for cold allodynia. TRPV3, TRPV4, TRPM2 and TRPM3 channels have also been of significant interest. This review discusses the preclinical promise and status of novel analgesic agents that target TRP channels and the challenges that these compounds may face in development and clinical practice.

LINKED ARTICLES

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

Authors+Show Affiliations

Hydra Biosciences, Cambridge, MA, USA.Clinical Laboratories, Baptist Medical Center, Jacksonville, FL, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28924972

Citation

Moran, Magdalene M., and Arpad Szallasi. "Targeting Nociceptive Transient Receptor Potential Channels to Treat Chronic Pain: Current State of the Field." British Journal of Pharmacology, vol. 175, no. 12, 2018, pp. 2185-2203.
Moran MM, Szallasi A. Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. Br J Pharmacol. 2018;175(12):2185-2203.
Moran, M. M., & Szallasi, A. (2018). Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. British Journal of Pharmacology, 175(12), 2185-2203. https://doi.org/10.1111/bph.14044
Moran MM, Szallasi A. Targeting Nociceptive Transient Receptor Potential Channels to Treat Chronic Pain: Current State of the Field. Br J Pharmacol. 2018;175(12):2185-2203. PubMed PMID: 28924972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. AU - Moran,Magdalene M, AU - Szallasi,Arpad, Y1 - 2017/11/06/ PY - 2017/02/13/received PY - 2017/08/27/revised PY - 2017/09/03/accepted PY - 2017/9/20/pubmed PY - 2019/8/7/medline PY - 2017/9/20/entrez SP - 2185 EP - 2203 JF - British journal of pharmacology JO - Br J Pharmacol VL - 175 IS - 12 N2 - : Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of transient receptor potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 cation channels as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically. TRPV1 channel antagonists have suffered from side effects related to the channel's role in temperature sensation; however, high dose formulations of capsaicin have reached the market and shown therapeutic utility. A number of potent, small molecule antagonists of TRPA1 channels have recently advanced into clinical trials for the treatment of inflammatory and neuropathic pain, and TRPM8 antagonists are following closely behind for cold allodynia. TRPV3, TRPV4, TRPM2 and TRPM3 channels have also been of significant interest. This review discusses the preclinical promise and status of novel analgesic agents that target TRP channels and the challenges that these compounds may face in development and clinical practice. LINKED ARTICLES: This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/28924972/Targeting_nociceptive_transient_receptor_potential_channels_to_treat_chronic_pain:_current_state_of_the_field_ L2 - https://doi.org/10.1111/bph.14044 DB - PRIME DP - Unbound Medicine ER -