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 inSNS–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 ofSNS–IKKβ−/−mice during stimulation with capsaicin or Formalin, specific activators of transient receptor potentials TRPV1 and TRPA1 calcium channels, respectively.In vitrostimulation of saphenous nerve preparations ofSNS–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.