title: Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.
abstract: Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury.
authors.affiliation: INSERM, UMR S 713, Paris, France; Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Meunier
authors.affiliation: INSERM, UMR S 677, Paris, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Latrémolière
authors.affiliation: INSERM, UMR S 713, Paris, France; Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dominguez
authors.affiliation: INSERM, UMR S 713, Paris, France; Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Mauborgne
authors.affiliation: LGN, UMR 7091, CNRS, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Philippe
authors.affiliation: INSERM, UMR S 677, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.affiliation: LGN, UMR 7091, CNRS, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.affiliation: INSERM, UMR S 713, Paris, France; Université Pierre et Marie Curie-Paris VI, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Benoliel
authors.affiliation: INSERM, UMR S 713, Paris, France; Université Pierre et Marie Curie-Paris VI, Paris, France. Electronic address: pohl@ext.jussieu.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Pohl