Human pharmacological approaches to TRP-ion-channel-based analgesic drug development

• Published in: Drug discovery today Vol. 23; no. 12; pp. 2003 - 2012
• Main Authors: Weyer-Menkhoff, Iris, Lötsch, Jörn
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2018
• Subjects: Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Drug Development - methods; Humans; Pain - drug therapy; Pain - metabolism; TRPV Cation Channels - metabolism
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2018.06.020

•High prevalence of persistent pain requires development of novel analgesics.•Preclinical research identified thermosensitive TRP channels as suitable targets.•Following preclinical research, >20 novel compounds have entered clinical testing.•The expression and function of thermoTRP channels are readily accessible in humans.•Many functional variants in TRP genes suggest future pharmacogenetic implications. The discovery of novel analgesic drug targets is an active research topic owing to insufficient treatment options for persisting pain. Modulators of temperature-sensing transient receptor potential ion channels (thermoTRPs), in particular TRPV1, TRPV2, TRPM8 and TRPA1, have reached clinical development. This requires access for TRP channels and the effects of specific modulators in humans. This is currently possible via (i) the study of TRP channel function in human-derived cell lines, (ii) immunohistochemical visualization of TRP channel expression in human tissues, (iii) human experimental pain models employing sensitization by means of topical application of TRP channel activators including capsaicin (TRPV1), menthol (TRPM8), mustard oil and cinnamaldehyde (TRPA1), and (iv) the study of phenotypic consequences of human TRP gene variants.