PT  - JOURNAL ARTICLE
AU  - Vanessa Bockhart
AU  - Cristina Elena Constantin
AU  - Annett Häussler
AU  - Nina Wijnvoord
AU  - Maike Kanngiesser
AU  - Thekla Myrczek
AU  - Geethanjali Pickert
AU  - Laura Popp
AU  - Jürgen-Markus Sobotzik
AU  - Manolis Pasparakis
AU  - Rohini Kuner
AU  - Gerd Geisslinger
AU  - Christian Schultz
AU  - Michaela Kress
AU  - Irmgard Tegeder
TI  - Inhibitor κB Kinase β Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity
AID  - 10.1523/JNEUROSCI.1496-09.2009
DP  - 2009 Oct 14
TA  - The Journal of Neuroscience
PG  - 12919--12929
VI  - 29
IP  - 41
4099  - http://www.jneurosci.org/content/29/41/12919.short
4100  - http://www.jneurosci.org/content/29/41/12919.full
SO  - J. Neurosci.2009 Oct 14; 29
AB  - Inhibitor κB kinase (IKK) regulates the activity of the transcription factor nuclear factor-κ 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 IKKβ in sensory neurons of the dorsal root ganglion (SNS–IKKβ−/−) 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–IKKβ−/− 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–IKKβ−/− 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–IKKβ−/− 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 IKKβ functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity.