The IKK-NF- B pathway: a source for novel molecular drug targets in pain therapy?

Several studies indicate that the nuclear factor-kappa B (NFB) -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 NFB in the nervous system, its impact on nociception, and several approaches that investigated the effects of various modulators of the classical IBkinase-NFB signal transduction pathway in inflammatory nociception and neuropathic pain. The results indicate that NFB has an impact on nociceptive transmission and processing and that a number of substances that inhibit the NFB-activating cascade are capable of reducing the nociceptive response in different animal models. Therefore, a modulation of specific participants in the NFB signal transduction might exert a useful approach for the development of new painkillers.—Niederberger, E., Geisslinger, G. The IKK-NFB pathway: a source for novel molecular drug targets in pain therapy? FASEB J. 22, 3432–3442 (2008)