The IKK-NF-κB pathway: a source for novel molecular drug targets in pain therapy? Ellen Niederberger 1 and Gerd Geisslinger Pharmazentrum Frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Germany 1 Correspondence: Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. E-mail: e.niederberger@em.uni-frankfurt.de Several studies indicate that the nuclear factor-kappa B (NF-κB) -activation cascade plays a crucial role not only in immune responses, inflammation, and apoptosis but also in the development and processing of pathological pain. Accordingly, a pharmacological intervention into this pathway may have antinociceptive effects and could provide novel treatment strategies for pain and inflammation. In this review we summarize the role of NF-κB in the nervous system, its impact on nociception, and several approaches that investigated the effects of various modulators of the classical I-κB-kinase-NF-κB signal transduction pathway in inflammatory nociception and neuropathic pain. The results indicate that NF-κB has an impact on nociceptive transmission and processing and that a number of substances that inhibit the NF-κB-activating cascade are capable of reducing the nociceptive response in different animal models. Therefore, a modulation of specific participants in the NF-κB signal transduction might exert a useful approach for the development of new painkillers.—Niederberger, E., Geisslinger, G. The IKK-NF-κB pathway: a source for novel molecular drug targets in pain therapy? Key Words: inflammation • nervous system • neuropathy
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