Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article | | Title | Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity. | | Author(s) | Bockhart V, Constantin CE, Häussler A, Wijnvoord N, Kanngiesser M, Myrczek T, Pickert G, Popp L, Sobotzik JM, Pasparakis M, Kuner R, Geisslinger G, Schultz C, Kress M, Tegeder I | | Institution | pharmazentrum frankfurt, Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Department of Clinical Pharmacology, Goethe University, 60590 Frankfurt, Germany. | | Source | J Neurosci 2009 Oct 14; 29(41):12919-29. | | MeSH | Animals
Ankyrins
Area Under Curve
Behavior, Animal
Calcium
Capsaicin
Cells, Cultured
Ganglia, Spinal
Gene Expression Regulation
I-kappa B Kinase
Ion Channel Gating
Membrane Potentials
Mice
Mice, Knockout
Motor Activity
Nerve Fibers, Unmyelinated
Neural Conduction
Nociceptors
Pain Measurement
Pain Threshold
Patch-Clamp Techniques
Physical Stimulation
Reaction Time
Sciatic Nerve
Sensory System Agents
Sodium Channel Blockers
Sodium Channels
TRPV Cation Channels
Tetrodotoxin
| | Abstract | Inhibitor kappaB kinase (IKK) regulates the activity of the transcription factor nuclear factor-kappa B that normally protects neurons against excitotoxicity. Constitutively active IKK is enriched at axon initial segments and nodes of Ranvier (NR). We used mice with a Cre-loxP-mediated specific deletion of IKKbeta in sensory neurons of the dorsal root ganglion (SNS-IKKbeta(-/-)) to evaluate whether IKK plays a role in sensory neuron excitability and nociception. We observed increased sensitivity to mechanical, cold, noxious heat and chemical stimulation in SNS-IKKbeta(-/-) mice, with normal proprioceptive and motor functions as revealed by gait analysis. This was associated with increased calcium influx and increased inward currents in small- and medium-sized primary sensory neurons of SNS-IKKbeta(-/-) mice during stimulation with capsaicin or Formalin, specific activators of transient receptor potentials TRPV1 and TRPA1 calcium channels, respectively. In vitro stimulation of saphenous nerve preparations of SNS-IKKbeta(-/-) mice showed increased neuronal excitability of A- and C-fibers but unchanged A- and C-fiber conduction velocities, normal voltage-gated sodium channel currents, and normal accumulation of ankyrin G and the sodium channels Nav1.6 at NR. The results suggest that IKKbeta functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19828806 |
|
|
| |
Advertise on this site.
| | |
|
