[The role of tetrodotoxin-resistant sodium channels in pain sensation studied on sns-knockout mice].
Nociceptive dorsal root ganglion neurons express sensory neuron-specific tetrodotoxin (TTX)-resistant voltage-gated sodium channel(SNS). The role of SNS in nociception has been studied by constructing sns-knockout mice. The sns-knockout mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, demonstrating that the slow TTX-resistant currents are mediated by the sns gene. The mutant mice were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive sodium channels demonstrated compensatory up-regulation of TTX-sensitive currents in DRG neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain sensation.
Ogata
N
N
Department of Physiology, Faculty of Medicine, Hiroshima University.
Yamamoto
M
M
Maruyama
H
H
D000818:Animals; D005727:Ganglia, Spinal / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D010146:Pain / Q000209:etiology* / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568318:Scn10a protein, mouse; D015222:Sodium Channels; D013779:Tetrodotoxin