Relationship Between the Firing Frequency of Injured Peripheral Neurons and Inhibition of Firing by Sodium Channel Blockers

Ritter, Amy M.; Ritchie, Courtney; Martin, William J.

doi:10.1016/j.jpain.2006.09.002

Cited by 14 publications

(14 citation statements)

References 48 publications

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“…However, both analyzed local anesthetic-insensitive Nav1.5-mutants (N406K and F1760A) displayed a preserved AJA sensitivity. 34 Another remarkable property of AJA observed in this study was an impressive shift of the voltage dependency of steady-state fast inactivation. A more critical analysis of our data indeed reveals further properties of AJA that support this notion: Use-dependent block by 3 μmol/L AJA was minimal and probably not relevant.…”

Section: Anesthesia and Analgesiamentioning

confidence: 54%

Inhibition of Voltage-Gated Na+ Channels by the Synthetic Cannabinoid Ajulemic Acid

Foadi

Berger²,

Pilawski³

et al. 2014

Anesthesia &Amp; Analgesia

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Section: Anesthesia and Analgesiamentioning

confidence: 54%

Inhibition of Voltage-Gated Na+ Channels by the Synthetic Cannabinoid Ajulemic Acid

Foadi

Berger²,

Pilawski³

et al. 2014

Anesthesia &Amp; Analgesia

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“…1F). In vivo, DRG neurons can fire tonically at 10 Hz for at least 1 hour, and in short bursts at frequencies of 30 Hz or more (41). Thus, the 3- to 10-Hz frequencies at which we were able to measure ATP release were well within the normal physiological range of firing for DRG neurons.…”

Section: Resultsmentioning

confidence: 99%

Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons

Fields

2010

Sci. Signal.

116

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The release of neuronal messengers outside synapses has broad biological implications, particularly with regard to communication between axons and glia. We identify a mechanism for nonsynaptic, nonvesicular release of adenosine triphosphate (ATP) from axons through volume-activated anion channels (VAACs) activated by microscopic axon swelling during action potential firing. We used a combination of single-photon imaging of ATP release, together with imaging for intrinsic optical signals, intracellular calcium ions (Ca2+), time-lapse video, and confocal microscopy, to investigate action potential–induced nonsynaptic release of this neurotransmitter. ATP release from cultured embryonic dorsal root ganglion axons persisted when bafilomycin or botulinum toxin was used to block vesicular release, whereas pharmacological inhibition of VAACs or prevention of action potential–induced axon swelling inhibited ATP release and disrupted activity-dependent signaling between axons and astrocytes. This nonvesicular, nonsynaptic communication could mediate various activity-dependent interactions between axons and nervous system cells in normal conditions, development, and disease.

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“…Tissue injury and inflammatory modulators can cause prolonged depolarization of peripheral nociceptors, and this probably contributes to inflammatory and neuropathic pain. A recent study suggests that the effectiveness of drugs at inhibiting peripheral nerve activity following nerve injury does not depend so much on the frequency at which action potentials are generated but rather on the nature of the injury and the pattern of action potential activity (Ritter et al, 2007). Given that a substantial degree of slow inactivation can be observed for TTX-R sodium channels at small, subthreshold membrane depolarizations without any spiking activity (Blair and Bean, 2003), a compound like lacosamide that targets the slow-inactivated channel might show enhanced therapeutic benefit.…”

Section: Inhibition Of Sensory Sodium Channels By Lacosamide 97mentioning

confidence: 99%

Differential Block of Sensory Neuronal Voltage-Gated Sodium Channels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine

Sheets

Heers²,

Stoehr³

et al. 2008

J Pharmacol Exp Ther

177

189

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Voltage-gated sodium channels play a critical role in excitability of nociceptors (pain-sensing neurons). Several different sodium channels are thought to be potential targets for pain therapeutics, including Na v 1.7, which is highly expressed in nociceptors and plays crucial roles in human pain and hereditary painful neuropathies, Na v 1.3, which is up-regulated in sensory neurons following chronic inflammation and nerve injury, and Na v 1.8, which has been implicated in inflammatory and neuropathic pain mechanisms. We compared the effects of lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], a new pain therapeutic, with those of lidocaine and carbamazepine on recombinant Na v 1.7 and Na v 1.3 currents and neuronal tetrodotoxin-resistant (Na v 1.8-type) sodium currents using whole-cell patch-clamp electrophysiology. Lacosamide is able to substantially reduce all three current types. However, in contrast to lidocaine and carbamazepine, 1 mM lacosamide did not alter steadystate fast inactivation. Inhibition by lacosamide exhibited substantially slower kinetics, consistent with the proposal that lacosamide interacts with slow-inactivated sodium channels. The estimated IC 50 values for inhibition by lacosamide of Na v 1.7-, Na v 1.3-, and Na v 1.8-type channels following prolonged inactivation were 182, 415, and 16 M, respectively. Na v 1.7-, Na v 1.3-, and Na v 1.8-type channels in the resting state were 221-, 123-, and 257-fold less sensitive, respectively, to lacosamide than inactivated channels. Interestingly, the ratios of resting to inactivated IC 50 s for carbamazepine and lidocaine were much smaller (ranging from 3 to 16). This suggests that lacosamide should be more effective than carbamazepine and lidocaine at selectively blocking the electrical activity of neurons that are chronically depolarized compared with those at more normal resting potentials.

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Relationship Between the Firing Frequency of Injured Peripheral Neurons and Inhibition of Firing by Sodium Channel Blockers

Cited by 14 publications

References 48 publications

Inhibition of Voltage-Gated Na+ Channels by the Synthetic Cannabinoid Ajulemic Acid

Inhibition of Voltage-Gated Na+ Channels by the Synthetic Cannabinoid Ajulemic Acid

Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons

Differential Block of Sensory Neuronal Voltage-Gated Sodium Channels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine

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