Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Na_v 1.7 mutation I234T.

ABSTRACT:

Background and purpose

Pharmacotherapy for pain currently involves trial and error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in the sodium channel, Na_v 1.7) used genomics, structural modelling and biophysical and pharmacological analyses to guide pharmacotherapy and showed that carbamazepine normalizes voltage dependence of activation of the Na_v 1.7-S241T mutant channel, reducing pain in patients carrying this mutation. However, whether this approach is applicable to other Na_v channel mutants is still unknown.

Experimental approach

We used structural modelling, patch clamp and multi-electrode array (MEA) recording to assess the effects of carbamazepine on Na_v 1.7-I234T muta

SUBMITTER: Yang Y 

PROVIDER: S-EPMC5980548 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature