Redox and trace metal regulation of ion channels in the pain pathway.
Given the clinical significance of pain disorders and the relative ineffectiveness of current therapeutics, it is important to identify alternative means of modulating nociception. The most obvious pharmacological targets are the ion channels that facilitate nervous transmission from pain sensors in the periphery to the processing regions within the brain and spinal cord. In order to design effective pharmacological tools for this purpose, however, it is first necessary to understand how these channels are regulated. A growing area of research involves the investigation of the role that trace metals and endogenous redox agents play in modulating the activity of a diverse group of ion channels within the pain pathway. In the present review, the most recent literature concerning trace metal and redox regulation of T-type calcium channels, NMDA (N-methyl-D-aspartate) receptors, GABAA (γ-aminobutyric acid A) receptors and TRP (transient receptor potential) channels are described to gain a comprehensive understanding of the current state of the field as well as to provide a basis for future thought and experimentation.
Department of Anesthesiology, Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A. Department of Neuroscience, Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
J Grayson
JG
Evans
Department of Anesthesiology, Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A. Department of Neuroscience, Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A. st9d@virginia.edu.
Slobodan M
SM
Todorovic
D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008959:Models, Neurological; D059225:Nociception / Q000502:physiology; D010084:Oxidation-Reduction; D010146:Pain / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D014131:Trace Elements / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism
D007473:Ion Channels; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D014131:Trace Elements; D050051:Transient Receptor Potential Channels; D008668:Metallothionein
ion channels; nociception; pain; pharmacology; redox agents; trace metals