Research article summary (published 12 Oct 2009):

Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity.

Full 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.

Author information

Author/s: Bockhart, Vanessa (V); Constantin, Cristina Elena (CE); Häussler, Annett (A); Wijnvoord, Nina (N); Kanngiesser, Maike (M); Myrczek, Thekla (T); Pickert, Geethanjali (G); Popp, Laura (L); Sobotzik, Jürgen-Markus (JM); Pasparakis, Manolis (M); Kuner, Rohini (R); Geisslinger, Gerd (G); Schultz, Christian (C); Kress, Michaela (M); Tegeder, Irmgard (I);

Affiliation: pharmazentrum frankfurt, Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Department of Clinical Pharmacology, Goethe University, 60590 Frankfurt, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 41) : pp 12919-29

Dates: Created 2009/10/15; Completed 2009/10/30;

PMID: 19828806, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Ankyrins - metabolism Area Under Curve Behavior, Animal Calcium - metabolism Capsaicin - pharmacology Cells, Cultured Ganglia, Spinal - cytology Gene Expression Regulation - genetics I-kappa B Kinase - deficiency Ion Channel Gating - drug effects; genetics Membrane Potentials - drug effects; genetics Mice Mice, Knockout Motor Activity - genetics

Motor Activity - genetics Nerve Fibers, Unmyelinated - drug effects; physiology Neural Conduction - genetics; physiology Nociceptors - drug effects; physiology Pain Measurement - methods Pain Threshold - physiology Patch-Clamp Techniques - methods Physical Stimulation - adverse effects Reaction Time - genetics Sciatic Nerve Sensory System Agents - pharmacology Sodium Channel Blockers - pharmacology Sodium Channels - genetics TRPV Cation Channels - physiology Tetrodotoxin - pharmacology

Associated Chemicals: Ankyrins (0) ; Sensory System Agents (0) ; Sodium Channel Blockers (0) ; Sodium Channels (0) ; TRPV Cation Channels (0) ; TRPV1 protein, mouse (0) ; sensory neuron specific (SNS) sodium channel (0) ; Ank3 protein, mouse (169242-13-1) ; Capsaicin (404-86-4) ; Tetrodotoxin (4368-28-9) ; Calcium (7440-70-2) ; I-kappa B Kinase (EC 2.7.1.37)

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