Inhibitor kappa B kinase beta dependent cytokine upregulation in nociceptive neurons contributes to nociceptive hypersensitivity after sciatic nerve injury

The Journal of Pain : Official Journal of the American Pain Society
Maike KanngiesserIrmgard Tegeder

Abstract

Inhibitor kappa B kinase (IKK)-mediated nuclear factor-kappa B (NF-κB) activation is a major pathway for transcriptional control of various pro-inflammatory factors. We here assessed whether activation of this pathway specifically in primary nociceptive neurons of the dorsal root ganglia (DRG) contributes to the development of nociceptive hypersensitivity. Mice carrying a cre-loxP-mediated deletion of inhibitor kappa B kinase beta (IKKβ) in DRG neurons were protected from nerve injury-evoked allodynia and hyperalgesia. This effect was mimicked by systemic treatment with an IKKβ inhibitor but was not observed upon specific inhibition of IKKβ in the spinal cord, suggesting a specific role of IKKβ in the peripheral neurons. The deletion of IKKβ in DRG neurons did not affect constitutive neuronal NF-κB activity, but reduced nerve injury-evoked NF-κB stimulation in the DRG and was associated with reduced upregulation of interleukin-16, monocyte chemoattractant protein-1/chemokine (CC motif) ligand 2 (MCP-1/CCL2), and tumor necrosis factor alpha (TNFα) in the DRG. These cytokines evoked a rapid rise of intracellular calcium in subsets of primary DRG neurons. The results suggest that IKKβ-mediated NF-κB stimulation in injured primary ...Continue Reading

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Citations

Jan 16, 2016·Journal of Molecular Neuroscience : MN·Liuming JiangTao Yang
May 23, 2015·Journal of Neuroinflammation·Christine V MöserEllen Niederberger
Oct 19, 2016·Neurobiology of Disease·Christine AltmannIrmgard Tegeder
Oct 25, 2016·Molecular Neurodegeneration·Christine AltmannIrmgard Tegeder
Jul 17, 2014·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Fuzhou WangRichard M Kream
May 26, 2020·Pharmacology & Therapeutics·Bao-Chun JiangYong-Jing Gao

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