Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury

Eugene S. Fu, Yan Ping Zhang, Jacqueline Sagen, Keith A. Candiotti, Paul D. Morton, Daniel J. Liebl, John R Bethea, Roberta Brambilla

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammatory processes in reactive glial cells. We utilized a transgenic mouse model (GFAP-IκBα-dn) where the classical NF-κB pathway is inactivated by overexpression of a dominant negative (dn) form of the inhibitor of kappa B (IκBα) in glial fibrillary acidic protein (GFAP)-expressing cells, which include astrocytes, Schwann cells, and satellite cells of the dorsal root ganglion (DRG) and sought to determine whether glial NF-κB inhibition leads to a reduction in pain behavior and inflammation following chronic constriction injury (CCI) of the sciatic nerve. As expected, following CCI nuclear translocation, and hence activation, of NF-κB was detected only in the sciatic nerve of wild type (WT) mice, and not in GFAP-IκBα-dn mice, while upregulation of GFAP was observed in the sciatic nerve and DRGs of both WT and GFAP-IκBα-dn mice, indicative of glial activation. Following CCI, mechanical and thermal hyperalgesia were reduced in GFAP-IκBα-dn mice compared to those in WT, as well as gene and protein expression of CCL2, CCR2 and CXCL10 in the sciatic nerve. Additionally, gene expression of TNF, CCL2, and CCR2 was reduced in the DRGs of transgenic mice compared to those of WT after CCI. We can therefore conclude that transgenic inhibition of NF-κB in GFAP-expressing glial cells attenuated pain and inflammation after peripheral nerve injury. These findings suggest that targeting the inflammatory response in Schwann cells and satellite cells may be important in treating neuropathic pain.

Original languageEnglish (US)
Pages (from-to)509-518
Number of pages10
JournalPain
Volume148
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Chronic constriction injury
  • NF-kappa B
  • Pain
  • Peripheral glia

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

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