| Autor: |
Möser, C.V., Möller, M., Fleck, S.C., Thomas, D., Geisslinger, G., Niederberger, E. |
| Přispěvatelé: |
Publica |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Popis: |
Inhibitor-kappaB kinase epsilon (IKKe, Ikbke) constitutes an NF-kB activating kinase with high homology to the classical I-kB kinase subunits, IKKa and IKKv. It is expressed in nociceptive neurons in the spinal cord and in dorsal root ganglia (DRG) and involved in inflammatory nociception. Under inflammatory conditions, IKKe deficient mice show significantly less nociceptive behavior in comparison to wild type mice associated with reduced activation of NF-kB and attenuated NF-kB-dependent gene expression. The role of IKKe in neuropathic pain has not been investigated so far. We applied the spared nerve injury (SNI) model of neuropathic pain in mice and found an increased expression of IKKe in the spinal cord, the DRGs and the sciatic nerve after induction of neuropathy. Genetic depletion of IKKe or pharmacological inhibition by amlexanox led to a significant reduction of mechanical hyperalgesia and cold allodynia in comparison to control mice. Transcription factor ELISA indicated that the effects are mediated by reduced activation of NF-kB. Furthermore, immunofluorescence staining, qPCR and Western Blot analyses revealed that the decreased pain-like behavior was associated with a reduced activation of microglia, diminished expression of c-fos as well as a decreased activation of MAP-Kinases. In summary, we conclude that IKKe modulates mechanisms of neuropathic pain by activating NF-kB. The administration of IKKe inhibitors might therefore constitute a new and promising approach for the therapy of neuropathic pain. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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