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The sensory neuron-specific sodium channel Na(v)1.8 and p38 mitogen-activated protein kinase are potential therapeutic targets within nociceptive dorsal root ganglion (DRG) neurons in inflammatory, and possibly neuropathic, pain. Na(v)1.8 channels within nociceptive DRG neurons contribute most of the inward current underlying the depolarizing phase of(More)
BACKGROUND Inherited erythermalgia (also termed "erythromelalgia"), characterized by episodic burning pain in the distal extremities evoked by warmth, has been causally linked with mutations of the Na(v)1.7 sodium channel, which is preferentially expressed in nociceptors. Thus far, Na(v)1.7 mutations within intracellular linker parts of the channel have(More)
Na(v)1.7 sodium channels can amplify weak stimuli in neurons and act as threshold channels for firing action potentials. Neurotrophic factors and pro-nociceptive cytokines that are released during development and under pathological conditions activate mitogen-activated protein kinases (MAPKs). Previous studies have shown that MAPKs can transduce(More)
Sodium channel Na(v)1.8 requires stronger depolarization than other sodium channels for activation and inactivation. The contribution of Na(v)1.8 C-terminus to this property was investigated by producing Na(v)1.8 and Na(v)1.4 chimeras and expressing them in ND7/23 cells. Current densities of the chimeras were significantly different than in parental(More)
BACKGROUND Sodium channel NaV1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of(More)
Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na v 1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium(More)
The Nav1.8 sodium channel isoform, expressed in sensory neurons and implicated in pain responses, is known to be upregulated in Xenopus oocytes by agents that activate protein kinase A. In the absence of exogenous modulators, Nav1.8 channels expressed in oocytes exhibited spontaneous downregulation, so that the amplitudes of peak sodium currents at the end(More)
The effects of fluoxetine (Prozac) on the transient A-currents (IA) in primary cultured hippocampal neurons were examined using the whole-cell patch clamp technique. Fluoxetine did not significantly decrease the peak amplitude of whole-cell K+ currents, but it accelerated the decay rate of inactivation, and thus decreased the current amplitude at the end of(More)
Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids (beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and lambda-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under(More)
Sodium channel Na(V)1.7, encoded by the SCN9A gene, is preferentially expressed in nociceptive primary sensory neurons, where it amplifies small depolarizations. In studies on a family with inherited erythromelalgia associated with Na(V)1.7 gain-of-function mutation A863P, we identified a nonsynonymous single-nucleotide polymorphism within SCN9A in the(More)