{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:00:18Z","timestamp":1791010818066,"version":"4.1.0"},"reference-count":53,"publisher":"Society for Neuroscience","issue":"7","license":[{"start":{"date-parts":[[2004,8,18]],"date-time":"2004-08-18T00:00:00Z","timestamp":1092787200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2004,2,18]]},"abstract":"<jats:p>Phosphorylation of I\u03baB through I\u03baB kinase (IKK) is the first step in nuclear factor \u03baB (NF-\u03baB) activation and upregulation of NF-\u03baB-responsive genes. Hence, inhibition of IKK activity may be expected to prevent injury-, infection-, or stress-induced upregulation of various proinflammatory genes and may thereby reduce hyperalgesia and inflammation. In the present study, we tested this hypothesis using a specific and potent IKK inhibitor (S1627). In an IKK assay, S1627 inhibited IKK activity with an IC<jats:sub>50<\/jats:sub>value of 10.0 \u00b1 1.2 n<jats:sc>m<\/jats:sc>. In cell culture experiments, S1627 inhibited interleukin (IL)-1\u03b2-stimulated nuclear translocation and DNA-binding of NF-\u03baB. Plasma concentration time courses after intraperitoneal injection revealed a short half-life of 2.8 hr in rats. Repeated intraperitoneal injections were, therefore, chosen as the dosing regimen. S1627 reversed thermal and mechanical hyperalgesia at 3\u00d7 30 mg\/kg in the zymosan-induced paw inflammation model and reduced the inflammatory paw edema at 3\u00d7 40 mg\/kg. S1627 also significantly reduced tactile and cold allodynia in the chronic constriction injury model of neuropathic pain at 30 mg\/kg once daily. The drug had no effect on acute inflammatory nociception in the formalin test and did not affect responses to heat and tactile stimuli in naive animals. As hypothesized, S1627 prevented the zymosan-induced nuclear translocation of NF-\u03baB in the spinal cord and the upregulation of NF-\u03baB-responsive genes including cyclooxygenase-2, tumor necrosis factor-\u03b1, and IL-1\u03b2. Our data indicate that IKK may prove an interesting novel drug target in the treatment of pathological pain and inflammation.<\/jats:p>","DOI":"10.1523\/jneurosci.3118-03.2004","type":"journal-article","created":{"date-parts":[[2004,2,18]],"date-time":"2004-02-18T20:02:48Z","timestamp":1077134568000},"page":"1637-1645","source":"Crossref","is-referenced-by-count":128,"title":["Specific Inhibition of I\u03baB Kinase Reduces Hyperalgesia in Inflammatory and Neuropathic Pain Models in 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