The role of Nav1.7 in electrogenesis in dorsal root ganglion (DRG) and sympathetic ganglion 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 and facilitating neural transmitter release.1–3 Nav1.7 dysfunction is associated with different human pain disorders. Gain-of-function missense mutations in Nav1.7 have been shown to cause primary erythermalgia and paroxysmal extreme pain disorder,4–7 while nonsense mutations in Nav1.7 result in loss of Nav1.7 function and a condition known as channelopathy-associated insensitivity to pain, a rare disorder in which affected individuals are unable to feel physical pain.8–11 A number of mediators, including prostaglandin,12 adenosine13 and serotonin,14 affect the electrophysiological properties of voltage-gated sodium channels. These mediators increase the magnitude of the current, lead to activation of the channel at more hyperpolarized potentials, and enhance the rates of channel activation and inactivation. As a consequence, hypersensitivity can sensitize nociceptive neurons. In an experimental model of inflammatory pain in which an irritant was injected into the hind paw in rats, Nav1.7 protein expression was upregulated within DRG neurons that project their axons to the inflamed area and such change increased excitability of these cells.15 Collectively, these data suggest that Nav1.7 contributes, at least in part, to pain associated with inflammation. Whether or not the stress (without inflammation) is one of the causes resulting in a dynamic change of Nav1.7 expression is unknown. “Nav1.7: stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus,” reported by Black et al,16 reveals a relationship between salty feeding and high level expression of Nav1.7 in supraoptic nucleus in rodent, which potentially provided a biological animal model to understand the relationship of stress and change of voltage gated sodium channel in irritable bowel syndrome (IBS). In the study, the rats were housed under a 12 hours-12 hours dark-light cycle, and fed with 2% NaCl (ad libitum) in their drinking water and unlimited access to food. The measurement of plasma osmotic pressure after such feeding was confirmed by hyperosmolarity (mOsm), i.e., 323.3 ± 4.8 in control rats, 353.2 ± 3.3 in salt-loaded rats (P < 0.05). The changes of Nav1.7 expression were analyzed using immunocytochemistry by comparing Nav1.7 immunofluorescence between two groups (6 control and 6 salt-loaded rats) after 7 days of salt loading. The authors found that salt-loading induced a substantial increase in the level of Nav1.7 immunoreactivity in magnocellular neurosecretory cells of the supraoptic nucleus compared to magnocellular neurosecretory cells in control rats. In addition to the detection of greater numbers of magnocellular neurosecretory cells that displayed Nav1.7 immunolabeling, the intensity of Nav1.7 in some magnocellular neurosecretory neurons was markedly greater than that observed in magnocellular neurosecretory cells from control rats. Quantification of the mean intensity of Nav1.7 signal within the circumscribed supraoptic nucleus demonstrated a significant up-regulation of Nav1.7 in response to salt-loading challenge. These observations demonstrate that the level of Nav1.7 protein in these cells is significantly increased in osmotically-challenged rats.