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

Abstract

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....