Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice

Two voltage gated sodium channels, Nav1.8 and Nav1.9, are exclusively expressed in primary sensory neurons and are suggested to play a role in different pain conditions, including chronic inflammatory and neuropathic pain states. Since no selective pharmacological tools are available, we investigated the involvement of Nav1.8 and Nav1.9 in pain transmission by the phenotypic characterization of Nav1.8 and Nav1.9 knockout mice and their wild-type littermates in models of acute nociception, peripheral inflammation and neuropathic pain. The present study provides evidence for a modulatory role of Nav1.9, and to a lesser extent Nav1.8 in the development of cold, but not mechanical allodynia in neuropathic pain conditions. Moreover, our results also indicate that Nav1.9 signaling might be involved in visceral pain. In contrast, the presumed critical role of these two sodium channel subtypes to inflammatory pain hypersensitivity seem, according to our results, to be limited and temporarily.