NaV1.7: Stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus

Background: Na(V)1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a peripheral sodium channel, and Na(V)1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects. However, occasional reports of patients with Na(V)1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, Na(V)1.2 and Na(V)1.6, display up-regulated expression in response to osmotic stress. Results: Here we show that Na(V)1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Na(V)1.7 immunoreactivity is increased in these cells in response to osmotic stress. Conclusions: Na(V)1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether Na(V)1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether Na(V)1.7 plays a functional role in human hypothalamus, is not yet known. Until these questions are resolved, the present findings suggest the need for careful assessment of hypothalamic function in patients with Na(V)1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as Na(V)1.7 blocking agents are studied.