The tetrodotoxin-resistant Na+ channel Nav1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice.
The tetrodotoxin-resistant sodium channel alpha subunit, Nav1.8, is exclusively expressed in primary sensory neurons and is suggested to play a role in the generation of ectopic action potentials after axonal injury and thereby contribute to neuropathic pain. Here we investigated the involvement of Nav1.8 in ectopic impulse generation in damaged axons by examining spontaneous activity and mechanosensitivity in neuromas formed by section of the saphenous nerve in Nav1.8 null mice and in their wild-type littermates. We recorded 522 identified units from 24 neuromas in vitro at two time points, 8-11 days (median 10 days) and 19-29 days (median 22 days) post-operatively. At approximately 10 days, neither genotype showed spontaneous activity, but a significantly higher proportion of fibres were mechanosensitive in wild-type (54%) compared to Nav1.8 null neuromas (18%). At approximately 22 days, 19% of fibres recorded in wild-type neuromas showed spontaneous activity, whereas only one fibre of the 238 (0. %) recorded in neuromas taken from null mice showed ongoing activity. In recordings at approximately 22 days, a similar proportion of fibres were mechanosensitive in wild-type and Nav1.8 null neuromas (51 and 46%, respectively). We conclude that Nav1.8 is essential for the expression of spontaneous activity in damaged sensory axons, and may also contribute to the development of ectopic mechanosensitivity.
Roza
Carolina
C
Department of Physiology, University of Alcalá, E-28871 Madrid, Spain.
Laird
Jennifer M A
JM
Souslova
Veronika
V
Wood
John N
JN
Cervero
Fernando
F
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019771:Axotomy; D004594:Electrophysiology; D005260:Female; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D009463:Neuroma / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568318:Scn10a protein, mouse; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin