Voltage-gated sodium channel mutations and painful neuropathy: Nav1.9 joins the family

In its simplest terms neuropathic pain arises as a consequence of hyperexcitability within the somatosensory nervous system. It is not surprising therefore that voltage-gated sodium channels (VGSCs), with their key role in regulating neuronal excitability, have come to the fore as pathophysiological factors in human neuropathic pain states. Not only can mutations in these ion channels lead to altered impulse generation/conduction in sensory neurons but they may also lead to degeneration of axon terminals. The VGSC family of proteins has nine members, of which Na_v1.7, Na_v1.8 and Na_v1.9 (encoded by the genesSCN9A, SCN 10A and SCN 11A, respectively) are preferentially expressed in peripheral neurons (Eijkelkamp et al., 2012). While gain of function variants of Na_v1.7 and Na_v1.8 have previously been reported in patients with painful peripheral neuropathy, in this issue of Brain, Huang et al.(2014) present the first evidence for a causative role of missense mutations in Na_v1.9 in painful neuropathy.

Brain 2014