Lentiviral-mediated targeted NF-κB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat

Alice Meunier, Alban Latremoliere, Elisa Dominguez, Annie Mauborgne, Stéphanie Philippe, Michel Hamon, Jacques Mallet, Jean Jacques Benoliel, Michel Pohl

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)687-697
Number of pages11
JournalMolecular Therapy
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Neuralgia
Sciatic Nerve
Neuroglia
Spinal Cord
Wounds and Injuries
Constriction
Peripheral Nerve Injuries
Pain
Nitric Oxide Synthase Type II
Chronic Pain
Interleukin-6
Transcription Factors
Central Nervous System
Inflammation
Genes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Lentiviral-mediated targeted NF-κB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat. / Meunier, Alice; Latremoliere, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean Jacques; Pohl, Michel.

In: Molecular Therapy, Vol. 15, No. 4, 01.04.2007, p. 687-697.

Research output: Contribution to journalArticle

Meunier, Alice ; Latremoliere, Alban ; Dominguez, Elisa ; Mauborgne, Annie ; Philippe, Stéphanie ; Hamon, Michel ; Mallet, Jacques ; Benoliel, Jean Jacques ; Pohl, Michel. / Lentiviral-mediated targeted NF-κB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat. In: Molecular Therapy. 2007 ; Vol. 15, No. 4. pp. 687-697.
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