The Novel Activity of Carbamazepine as an Activation Modulator Extends from Na1.7 Mutations to the Na1.8-S242T Mutant Channel from a Patient with Painful Diabetic Neuropathy.

Neuropathic pain in patients carrying sodium channel gain-of-function mutations is generally refractory to pharmacotherapy. However, we have shown that pretreatment of cells with clinically achievable concentration of carbamazepine (CBZ; 30 M) depolarizes the voltage dependence of activation in some Na1.7 mutations such as S241T, a novel CBZ mode of action of this drug.

A SCN10A SNP biases human pain sensitivity.

Background: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined.

Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli.

Unlabelled: Voltage-gated sodium channel Nav1.7 is a central player in human pain. Mutations in Nav1.

The G1662S NaV1.8 mutation in small fibre neuropathy: impaired inactivation underlying DRG neuron hyperexcitability.

Objective: Painful small fibre neuropathy (SFN) represents a significant public health problem, with no cause apparent in one-half of cases (termed idiopathic, I-SFN). Gain-of-function mutations of sodium channel NaV1.7 have recently been identified in nearly 30% of patients with biopsy-confirmed I-SFN.

Differential effect of D623N variant and wild-type Na(v)1.7 sodium channels on resting potential and interspike membrane potential of dorsal root ganglion neurons.

Sodium channel NaV1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function NaV1.