title: T-type voltage-gated calcium channels as targets for the development of novel pain therapies.
abstract: It is well recognized that voltage-gated calcium (Ca(2+)) channels modulate the function of peripheral and central pain pathways by influencing fast synaptic transmission and neuronal excitability. In the past, attention focused on the modulation of different subtypes of high-voltage-activated-type Ca(2+) channels; more recently, the function of low-voltage-activated or transient (T)-type Ca(2+) channels (T-channels) in nociception has been well documented. Currently, available pain therapies remain insufficient for certain forms of pain associated with chronic disorders (e.g. neuropathic pain) and often have serious side effects. Hence, the identification of selective and potent inhibitors and modulators of neuronal T-channels may help greatly in the development of safer, more effective pain therapies. Here, we summarize the available information implicating peripheral and central T-channels in nociception. We also discuss possible future developments aimed at selective modulation of function of these channels, which are highly expressed in nociceptors.
authors.affiliation: Department of Anesthesiology and Neuroscience, University of Virginia School of Medicine, Charlottesville, 22908-0710, USA. st9d@virginia.edu
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Todorovic
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D058990:Molecular Targeted Therapy; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
chemical_list: D000700:Analgesics; D020747:Calcium Channels, T-Type; D063385:Cannabinoid Receptor Modulators; D016718:Arachidonic Acid; D019204:GTP-Binding Proteins