Paroxysmal extreme pain disorder (PEPD) is an autosomal dominant pain syndrome characterized by severe pain attacks and skin redness already in infancy. It is caused by gain-of-function mutations of the voltage dependent sodium channel Nav1.7 (SCN9A). 
So far, about ten of these mutations have been described. In electrophysiological recordings, the mutated sodium channels often show impaired inactivation and increased persistent current. Therapeutic options include antiepileptic drugs such as Carbamazepine, or Amitriptyline and Clonidine. However, treatment is often unsatisfactory. 

Here, we describe the functional characterization of a previously unknown SCN9A mutation (M1628K) in a patient diagnosed with PEPD. This mutation was not described yet and resides next to the previously described PEPD mutant M1627K. We screened over 350 approved active drug compounds with the help of an automated patch-clamp system, to identify potential therapeutics to treat the hyper-functional phenotype of the M1628K mutation. 

The newly described PEPD mutation M1628K shows a shift in inactivation similar to the previously described mutations, but differs concerning time to peak and current decay.  Using the automated patch-clamp system, approved drugs were identified that specifically modulate this mutation and thus may be candidates for repurposing in the future.