Abstract
Two voltage gated sodium channel α-subunits, Nav1.7 and Nav1.8, are expressed at high levels in nociceptor terminals and have been implicated in the development of inflammatory pain. Mis-expression of voltage-gated sodium channels by damaged sensory neurons has also been implicated in the development of neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain. Here we show that deleting Nav1.7 has no effect on the development of neuropathic pain. Double knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic pain, despite a lack of inflammatory pain symptoms and altered mechanical and thermal acute pain thresholds. These studies demonstrate that, in contrast to the highly significant role for Nav1.7 in determining inflammatory pain thresholds, the development of neuropathic pain does not require the presence of either Nav1.7 or Nav1.8 alone or in combination.
Highlights
Voltage gated sodium channels (VGSC) underlie the electrical excitability of nerve and muscle
Many loss- as well as gain-of-function mutations of α-subunits have been identified in human conditions characterised with epilepsy, seizures, ataxia and increased sensitivity to pain
In the present study we investigated the role of the Nav1.7 channel in neuropathic pain using nociceptor-specific deletion of Nav1.7 in mouse
Summary
Voltage gated sodium channels (VGSC) underlie the electrical excitability of nerve and muscle. VGSCs consist of pore forming α-subunits and auxiliary β-subunits. The β-subunits modulate the localisation, expression and functional properties of α-subunits [1]. Different α-subunits have distinct electrophysiological and pharmacological properties [2]. The complex pattern of expression of α-subunits may imply special roles for particular subunits in different cell types [3]. Many loss- as well as gain-of-function mutations of α-subunits have been identified in human conditions characterised with epilepsy, seizures, ataxia and increased sensitivity to pain. This suggests that mutations of VGSC in humans are significant factors in aetiology of neuronal diseases [4]
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