Internal medicine

Nociception

Neuroscience

Receptor

Nociceptor

Organic chemistry

Psychoanalysis

Transient receptor potential channel

Psychology

Chemistry

Neuropathic pain

Hyperalgesia

Sodium channel

Sodium

Confusion

Anesthesia

Addiction

Medicine

Pharmacology

Nature reviews. Neuroscience

Emerging evidence suggests a role for the voltage-gated sodium channel NaV1.9 in pain. In this Progress article, Dib-Hajj, Black and Waxman analyse the findings from three studies that report mutations in the gene encoding NaV1.9 in pain disorders, and suggest that NaV1.9 may be a potential therapeutic target for pain. 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.

NaV1.9: a sodium channel linked to human pain