RGD Reference Report - Inhibitor kappa B kinase beta dependent cytokine upregulation in nociceptive neurons contributes to nociceptive hypersensitivity after sciatic nerve injury. - Rat Genome Database

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

Authors: Kanngiesser, M  Haussler, A  Myrczek, T  Kusener, N  Lim, HY  Geisslinger, G  Niederberger, E  Tegeder, I 
Citation: Kanngiesser M, etal., J Pain. 2012 May;13(5):485-97. doi: 10.1016/j.jpain.2012.02.010.
RGD ID: 8549487
Pubmed: PMID:22564672   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jpain.2012.02.010   (Journal Full-text)

Inhibitor kappa B kinase (IKK)-mediated nuclear factor-kappa B (NF-kappaB) 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 (IKKbeta) in DRG neurons were protected from nerve injury-evoked allodynia and hyperalgesia. This effect was mimicked by systemic treatment with an IKKbeta inhibitor but was not observed upon specific inhibition of IKKbeta in the spinal cord, suggesting a specific role of IKKbeta in the peripheral neurons. The deletion of IKKbeta in DRG neurons did not affect constitutive neuronal NF-kappaB activity, but reduced nerve injury-evoked NF-kappaB 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 (TNFalpha) in the DRG. These cytokines evoked a rapid rise of intracellular calcium in subsets of primary DRG neurons. The results suggest that IKKbeta-mediated NF-kappaB stimulation in injured primary sensory neurons promotes cytokine and chemokine production and contributes thereby to the development of chronic pain. PERSPECTIVE: Inhibitors of IKK that do not pass the blood-brain barrier and act only in the periphery might be useful for reduction of the pro-inflammatory response in peripheral DRG neurons and reduce thereby nerve injury-evoked pain without affecting neuroprotective effects of NF-kappaB in the central nervous system.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCL2Humansciatic neuropathy  ISOCcl2 (Mus musculus)protein:increased expression:lumbar dorsal root ganglion (mouse)RGD 
Ccl2Ratsciatic neuropathy  ISOCcl2 (Mus musculus)protein:increased expression:lumbar dorsal root ganglion (mouse)RGD 
Ccl2Mousesciatic neuropathy  IEP protein:increased expression:lumbar dorsal root ganglion (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information