The IKK-NF-kappaB pathway: a source for novel molecular drug targets in pain therapy?
Several studies indicate that the nuclear factor-kappa B (NF-kappaB) -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-kappaB in the nervous system, its impact on nociception, and several approaches that investigated the effects of various modulators of the classical I-kappaB-kinase-NF-kappaB signal transduction pathway in inflammatory nociception and neuropathic pain. The results indicate that NF-kappaB has an impact on nociceptive transmission and processing and that a number of substances that inhibit the NF-kappaB-activating cascade are capable of reducing the nociceptive response in different animal models. Therefore, a modulation of specific participants in the NF-kappaB signal transduction might exert a useful approach for the development of new painkillers.
Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. e.niederberger@em.uni-frankfurt.de
Ellen
E
Niederberger
Gerd
G
Geisslinger
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000700:Analgesics; D016328:NF-kappa B; D051550:I-kappa B Kinase