In this study we have demonstrated that NaV1.7 is present within neurons within the hypothalamic supraoptic nucleus, specifically within vasopressin- and oxytocin-producing magnocellular neurosecretory neurons. We also show that the level of NaV1.7 protein in these cells is not fixed but, on the contrary, is dynamic, increasing as a result of salt-loading.
A role NaV1.7 in electrogenesis in DRG neurons is well-established, and it is clear that NaV1.7 functions as a threshold channel in these neurons, amplifying small depolarizing inputs to bring the cell to threshold for action potential generation [26, 27] and possibly facilitating invasion into, and/or transmitter release from, preterminal axons within the spinal cord dorsal horn [1, 28]. In contrast, a functional role of NaV1.7 within supraoptic neurons is less well understood. Action potential bursts, triggered by osmotic changes, lead to release of vasopressin by supraoptic magnocellular neurons  and it is known that tetrodotoxin-sensitive sodium channels contribute to this bursting [20–22].
Supraoptic magnocellular neurons are known to be highly dynamic. It is known that, in response to changes in osmolality, the expression of peptides within these cells changes, and they change in size . In parallel, it has been shown that in response to increased osmolarity there are changes in deployment of sodium channels, with up-regulated expression of the NaV1.2 and NaV1.6 alpha subunits, and of the sodium channel beta-1 and beta-2 subunits [24, 25]. The present results show that the level of NaV1.7 protein, like that of NaV1.2 and NaV1.6 [24, 25], is dynamic, and is up-regulated within supraoptic magnocellular neurons exposed to osmotic stress via salt-loading. A previous study  demonstrated an increase in the amplitude of the transient Na+ current, and an even greater increase in the amplitude and density of the Na+ currents evoked by slow ramp stimuli in supraoptic neurons following salt-loading. While definitive identification of the current as NaV1.7 current would require specific blockade or knockout, both of these types of current have been observed to be produced by NaV1.7 . Because NaV1.7 is present within vasopressin neurons, it seems likely that this sodium channel isoform plays some role in vasopressin release in response to the osmotic stress imposed by salt-loading.
Although only low levels of NaV1.7 have been reported in the hypothalamus in primates , it is possible that the density of NaV1.7 channels within magnocellular neurons of the human supraoptic nucleus, like that in rodents, is subject to up-regulation in response to some forms of stress. NaV1.7 blockers are currently under development as potential pharmacotherapeutics for pain [30–34]. Hypothalamic dysfunction has not been observed thus far in families with channelopathy-associated insensitivity to pain due to null mutations in the gene encoding NaV1.7. However, functional NaV1.7 channels are absent beginning in early embryogenesis in affected individuals in these families, and the possibility that there might be compensatory changes in hypothalamic neurons which maintain relatively normal function in these cells cannot be excluded. Whether levels of NaV1.7 are increased in response to environmental factors or stress within the human hypothalamus, and whether NaV1.7 plays a functional role in hypothalamic neurons in humans, is not known. Until these questions are resolved, the present findings suggest the need for assessment of hypothalamic function in patients carrying NaV1.7 mutations especially when subjected to stress, and for monitoring of hypothalamic function as NaV1.7 blocking agents are studied.