TRP channels and analgesia.
Since cloning and characterizing the first nociceptive ion channel Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1), other TRP channels involved in nociception have been cloned and characterized, which include TRP Vanilloid 2 (TRPV2), TRP Vanilloid 3 (TRPV3), TRP Vanilloid 4 (TRPV4), TRP Ankyrin 1 (TRPA1) and TRP Melastatin 8 (TRPM8), more recently TRP Canonical 1, 5, 6 (TRPC1, 5, 6), TRP Melastatin 2 (TRPM2) and TRP Melastatin 3 (TRPM3). These channels are predominantly expressed in C and Aδ nociceptors and transmit noxious thermal, mechanical and chemical sensitivities. TRP channels are modulated by pro-inflammatory mediators, neuropeptides and cytokines. Significant advances have been made targeting these receptors either by antagonists or agonists to treat painful conditions. In this review, we will discuss TRP channels as targets for next generation analgesics and the side effects that may ensue as a result of blocking/activating these receptors, because they are also involved in physiological functions such as release of vasoactive neuropeptides and regulation of vascular tone, maintenance of the body temperature, gastrointestinal motility, urinary bladder control, etc.
Department of Pharmacology, Southern Illinois University School of Medicine Springfield, IL 62702, USA. lpremkumar@siumed.edu
Louis S
LS
Premkumar
Mruvil
M
Abooj
D000698:Analgesia; D017487:Ankyrins / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009619:Nociceptors / Q000502:physiology*; D050053:TRPM Cation Channels / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000502:physiology*
D017487:Ankyrins; D050053:TRPM Cation Channels; C475667:TRPM3 protein, human; C425966:TRPM8 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C400769:TRPV2 protein, human; C459445:TRPV3 protein, human; C416986:TRPV4 protein, human; D050051:Transient Receptor Potential Channels