Painful Na-channelopathies: an expanding universe

•The universe of painful Na-channelopathies is expanding.•Na-channel mutations cause common painful neuropathies as well as rare genetic pain disorders.•Mutations of NaV1.8, as well as NaV1.7, can cause painful channelopathies.

The universe of painful Na-channelopathies – human disorders caused by mutations in voltage-gated sodium channels – has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic ‘model disorders’ such as inherited erythromelalgia and channelopathy-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic.