In behavioral experiments, inhibition of nuclear factor-kappaB activation by systemic administration of the IkappaB kinase inhibitor S1627 has been shown to attenuate inflammatory and neuropathic pain. Here, we specifically investigated with electrophysiological recordings in anesthetized rats whether spinal application of S1627 influences hyperexcitability of dorsal horn neurons during an acute knee joint inflammation. Spinal application of S1627 before and early during development of inflammation totally prevented spinal hyperexcitability suggesting an important role of spinal nuclear factor-kappaB in this process. During established inflammation, however, S1627 did not reduce the responses of neurons to mechanical stimulation of the inflamed knee within 2.5 h after spinal administration, thus suggesting that spinal hyperexcitability is not maintained by continuous nuclear factor-kappaB activation.