title: Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics.
abstract: The last decade has witnessed an explosion in novel findings relating to the molecules involved in mediating the sensation of pain in humans. Transient receptor potential (TRP) ion channels emerged as the greatest group of molecules involved in the transduction of various physical stimuli into neuronal signals in primary sensory neurons, as well as, in the development of pain. Here, we review the role of TRP ion channels in primary sensory neurons in the development of pain associated with peripheral pathologies and possible strategies to translate preclinical data into the development of effective new analgesics. Based on available evidence, we argue that nociception-related TRP channels on primary sensory neurons provide highly valuable targets for the development of novel analgesics and that, in order to reduce possible undesirable side effects, novel analgesics should prevent the translocation from the cytoplasm to the cell membrane and the sensitization of the channels rather than blocking the channel pore or binding sites for exogenous or endogenous activators.
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Sousa-Valente
authors.forename: A P
authors.initials: AP
authors.lastname: Andreou
authors.forename: L
authors.initials: L
authors.lastname: Urban
authors.forename: I
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D017288:Pain Threshold / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D049990:Membrane Transport Modulators; D050051:Transient Receptor Potential Channels
keywords: TRPA1; TRPM2; TRPM3; TRPM8; TRPV1; TRPV4; inflammation; nerve injury; pain