From genes to pain: Na v 1.7 and human pain disorders.
Gain-of-function mutations or dysregulated expression of voltage-gated sodium channels can produce neuronal hyperexcitability, leading to acute or chronic pain. The sodium channel Na(v)1.7 is expressed preferentially in most slowly conducting nociceptive neurons and in sympathetic neurons. Gain-of-function mutations in the Na(v)1.7 channel lead to DRG neuron hyperexcitability associated with severe pain, whereas loss of the Na(v)1.7 channel in patients leads to indifference to pain. The contribution of Na(v)1.7 to acquired and inherited pain states and the absence of motor, cognitive and cardiac deficits in patients lacking this channel make it an attractive target for the treatment of neuropathic pain.
Dib-Hajj
Sulayman D
SD
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cummins
Theodore R
TR
Black
Joel A
JA
Waxman
Stephen G
SG
D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D023421:Models, Animal; D009154:Mutation; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009474:Neurons / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics*; D013001:Somatoform Disorders / Q000235:genetics* / Q000503:physiopathology*
D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels