title: Glial NF-κB inhibition alters neuropeptide expression after sciatic nerve injury in mice.
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Fu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sagen
authors.forename: Roy C
authors.initials: RC
authors.lastname: Levitt
authors.forename: Keith A
authors.initials: KA
authors.lastname: Candiotti
authors.forename: John R
authors.initials: JR
authors.lastname: Bethea
authors.forename: Roberta
authors.initials: R
authors.lastname: Brambilla
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003251:Constriction, Pathologic / Q000378:metabolism; D019004:Galanin / Q000096:biosynthesis; D005727:Ganglia, Spinal / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis*; D012584:Sciatic Nerve / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C528900:glial fibrillary astrocytic protein, mouse; D019004:Galanin; D015740:Calcitonin Gene-Related Peptide