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Pain Med. 2009 Oct;10(7):1260-9. doi: 10.1111/j.1526-4637.2009.00719.x.

Voltage-gated sodium channels: therapeutic targets for pain.

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  • 1Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06520-8018, USA.

Abstract

OBJECTIVE:

To provide an overview of the role of voltage-gated sodium channels in pathophysiology of acquired and inherited pain states, and of recent developments that validate these channels as therapeutic targets for treating chronic pain.

BACKGROUND:

Neuropathic and inflammatory pain conditions are major medical needs worldwide with only partial or low efficacy treatment options currently available. An important role of voltage-gated sodium channels in many different pain states has been established in animal models and, empirically, in humans, where sodium channel blockers partially ameliorate pain. Animal studies have causally linked changes in sodium channel expression and modulation that alter channel gating properties or current density in nociceptor neurons to different pain states. Biophysical and pharmacological studies have identified the sodium channel isoforms Na(v)1.3, Na(v)1.7, Na(v)1.8, and Na(v)1.9 as particularly important in the pathophysiology of different pain syndromes. Recently, gain-of-function mutations in SCN9A, the gene which encodes Na(v)1.7, have been linked to two human-inherited pain syndromes, inherited erythromelalgia and paroxysmal extreme pain disorder, while loss-of-function mutations in SCN9A have been linked to complete insensitivity to pain. Studies on firing properties of sensory neurons of dorsal root ganglia demonstrate that the effects of gain-of-function mutations in Na(v)1.7 on the excitability of these neurons depend on the presence of Na(v)1.8, which suggests a similar physiological interaction of these two channels in humans carrying the Na(v)1.7 pain mutation.

CONCLUSIONS:

These studies suggest that isoform-specific blockers of these channels or targeting of their modulators may provide novel approaches to treatment of pain.

PMID:
19818036
[PubMed - indexed for MEDLINE]
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