Seminar - The role of the voltage gated sodium channel Nav1.7 in human pain and pleasure


McIntyre Medical Building Room 1034, 3655 promenade Sir William Osler, Montreal, QC, H3G 1Y6, CA

There has been significant progress over the last decade in understanding the molecular basis by which sensory neurons transduce and subsequently transmit noxious (ie. tissue damaging) stimuli giving rise to the sensation of pain. Over this same period we have recognized that mutations in such ion channels (many of which are selectively expressed in sensory neurons) can result in inherited pain disorders in humans. An excellent example is the voltage gated ion channel NaV 1.7 encoded by the gene SCN9a. Loss of function mutations in this ion channel result in congenital inability to experience pain due to reduced excitability of nociceptors. Gain of function mutations can cause a number of distinct neuropathic pain disorders including erythromelalgia, paroxysmal extreme pain disorder and more common variants have recently been linked to painful diabetic neuropathy. The effects of Nav1.7 are not however restricted to nociceptors as C-low threshold mechanoreceptors also express high levels of Nav1.7. These afferents are implicated in affective touch and indeed although patients with loss of function mutations in Nav1.7 have normal discriminative touch, affective touch induced by stroking of hairy skin is impaired. C-LTMR afferents lacking Nav1.7 show an increased mechanical threshold and altered stimulus response function. In summary Nav1.7 has a dual role: not only is it essential for pain perception but also affective touch through the regulation of excitability of nociceptors and C-LTMRs respectively.

This event is co-sponsored by the Alan Edwards Centre for Research on Pain (AECRP) and the Quebec Pain Research Network (QPRN).