Nav1.8 is expressed specifically in the dorsal root ganglion (DRG), in unmyelinated, small-diameter sensory neurons called C-fibres, and is involved in nociception.

The specific location of Nav1.8 in sensory neurons of the DRG may make it a key therapeutic target for the development of new analgesics[11] and the treatment of chronic pain.

Voltage clamp methods have demonstrated that NaV1.8 is unique, among sodium channels, in exhibiting relatively depolarized steady-state inactivation.

However, Nav1.8 is cold-resistant and is able to generate action potentials in the cold to carry information from nociceptors to the central nervous system (CNS).

Therefore, nociceptors are easily sensitised by agents such as bradykinin and nerve growth factor, which are released at the site of tissue injury, ultimately causing changes to ion channel conductance.

[28] Prostaglandins such as PGE2 can sensitise nociceptors to thermal, chemical and mechanical stimuli and increase the excitability of DRG sensory neurons.

This isoform is activated by the inflammatory mediator bradykinin and phosphorylates Nav1.8, causing an increase in sodium current in the sensory neurons, which promotes mechanical hyperalgesia.

[39] The increased levels of nerve growth factor and tumour necrosis factor-α (TNF-α) causes the upregulation of Nav1.8 in sensory neurons via the accessory protein p11 (annexin II light chain).

It has been shown using the yeast-two hybrid screening method that p11 binds to a 28-amino-acid fragment at the N terminus of Nav1.8 and promotes its translocation to the plasma membrane.

[40] p11-null nociceptive sensory neurons in mice, created using the Cre-loxP recombinase system, show a decrease in Nav1.8 expression at the plasma membrane.

A gain-of-function mutation in Nav1.7 located in the DRG sensory neurons was found in nearly 30% of patients with idiopathic small fiber neuropathy in one study.