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Glial NF-kappa B inhibition alters neuropeptide expression after sciatic nerve injury in mice
Journal article   Open access   Peer reviewed

Glial NF-kappa B inhibition alters neuropeptide expression after sciatic nerve injury in mice

Yan Ping Zhang, Eugene S. Fu, Jacqueline Sagen, Roy C. Levitt, Keith A. Candiotti, John R. Bethea and Roberta Brambilla
Brain research, v 1385, pp 38-46
18 Apr 2011
PMID: 21352816
url
https://europepmc.org/articles/pmc4292841View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

Astrocytes Chronic constriction injury Inflammation Neuropathic pain
We utilized a transgenic mouse model where nuclear factor kappa B (NF-κB) is selectively inhibited in glial fibrillary acidic protein (GFAP) expressing cells. The transgene, GFAP-IκBα-dn, overexpresses a dominant negative form of the inhibitor of NF-κB (IκBα) under the control of the GFAP promoter. In the present work, we sought to understand the impact of glial NF-κB inhibition on the expression of pain mediating sensory neuropeptides galanin and calcitonin gene related peptide (CGRP) in a model of neuropathic pain in mice. Chronic constriction injury (CCI) of the left sciatic nerve was performed on wild type (WT) and GFAP-IκBα-dn transgenic mice. RT-PCR and immunohistological staining were performed in sciatic nerve and/or L4-L5 DRG tissue for galanin, CGRP and macrophage marker CD11b. GFAP-IκBα-dn mice had less mechanical and thermal hyperalgesia compared to WT mice post-CCI. After CCI, we observed galanin upregulation in DRG and sciatic nerve, which was less in GFAP-IκBα-dn mice. CGRP gene expression in the DRG increased transiently on day 1 post-CCI in WT but not in GFAP-IκBα-dn mice, and no evidence of CGRP upregulation in sciatic nerve post-CCI was found. After CCI, upregulation of CD11b in sciatic nerve was less in GFAP-IκBα-dn mice compared to WT mice, indicative of less macrophage infiltration. Our results showed that glial NF-κB inhibition reduces galanin and CGRP expression, which are neuropeptides that correlate with pain behavior and inflammation after peripheral nerve injury. ► We studied neuropeptide expression after peripheral nerve injury in mice. ► Galanin and CGRP are neuropeptides that correlate with pain and inflammation. ► Glial NF-kappa B inhibition alters expression of galanin and CGRP. ► Glial NF-kappa B inhibition alters macrophage infiltration.

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