NaV1.9: a sodium channel linked to human pain

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Abstract

The voltage-gated sodium channel NaV1.9 is preferentially expressed in nociceptors and has been shown in rodent models to have a major role in inflammatory and neuropathic pain. These studies suggest that by selectively targeting NaV1.9, it might be possible to ameliorate pain without inducing adverse CNS side effects such as sedation, confusion and addictive potential. Three recent studies in humans — two genetic and functional studies in rare genetic disorders, and a third study showing a role for NaV1.9 in painful peripheral neuropathy — have demonstrated that NaV1.9 plays an important part both in regulating sensory neuron excitability and in pain signalling. With this human validation, attention is turning to this channel as a potential therapeutic target for pain.

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Figure 1: Distribution of NaV1.9 in primary afferents.
Figure 2: NaV1.9 increases the excitability of DRG neurons.
Figure 3: Schematic diagram of the NaV1.9 channel and locations of substitutions identified in individuals with pain disorders.
Figure 4: Voltage-clamp and current-clamp analyses of NaV1.9 I381T mutant channels.

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Acknowledgements

The authors thank the members of their group for valuable discussions. Work in the authors' laboratory is supported in part by grants from the US Rehabilitation Research and Development Service and Medical Research Service, the US Department of Veterans Affairs and the Erythromelalgia Association. The Center for Neuroscience and Regeneration Research is a collaboration of the Paralyzed Veterans of America with Yale University, New Haven, Connecticut, USA.

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Correspondence to Stephen G. Waxman.

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Dib-Hajj, S., Black, J. & Waxman, S. NaV1.9: a sodium channel linked to human pain. Nat Rev Neurosci 16, 511–519 (2015) doi:10.1038/nrn3977

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