Regulating excitability of peripheral afferents: emerging ion channel targets.
The transmission and processing of pain signals relies critically on the activities of ion channels that are expressed in afferent pain fibers. This includes voltage-gated channels, as well as background (or leak) channels that collectively regulate resting membrane potential and action potential firing properties. Dysregulated ion channel expression in response to nerve injury and inflammation results in enhanced neuronal excitability that underlies chronic neuropathic and inflammatory pain. Pharmacological modulators of ion channels, particularly those that target channels on peripheral neurons, are being pursued as possible analgesics. Over the past few years, a number of different types of ion channels have been implicated in afferent pain signaling. Here we give an overview of recent advances on sodium, calcium, potassium and chloride channels that are emerging as especially attractive targets for the treatment of pain.
1] Center for Neuroscience & Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Veterans Affairs Medical Center, West Haven, Connecticut, USA.
Stephen G
SG
Waxman
Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Gerald W
GW
Zamponi
D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D010146:Pain / Q000473:pathology*; D010525:Peripheral Nerves / Q000503:physiopathology*
D007473:Ion Channels