title: Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice.
abstract: Mechanisms underlying central neuropathic pain are poorly understood. Although glial dysfunction has been functionally linked with neuropathic pain, very little is known about modulation of pain by oligodendrocytes. Here we report that genetic ablation of oligodendrocytes rapidly triggers a pattern of sensory changes that closely resemble central neuropathic pain, which are manifest before overt demyelination. Primary oligodendrocyte loss is not associated with autoreactive T- and B-cell infiltration in the spinal cord and neither activation of microglia nor reactive astrogliosis contribute functionally to central pain evoked by ablation of oligodendrocytes. Instead, light and electron microscopic analyses reveal axonal pathology in the spinal dorsal horn and spinothalamic tract concurrent with the induction and maintenance of nociceptive hypersensitivity. These data reveal a role for oligodendrocytes in modulating pain and suggest that perturbation of oligodendrocyte functions that maintain axonal integrity can lead to central neuropathic pain independent of immune contributions.
authors.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Gritsch
authors.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Jianning
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thilemann
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Wörtge
authors.affiliation: 1] Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany [2] Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bruttger
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
authors.forename: Khalad
authors.initials: K
authors.lastname: Karram
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Ruhwedel
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Blanfeld
authors.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vardeh
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany.
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D001253:Astrocytes; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D001402:B-Lymphocytes; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D017628:Microglia; D008854:Microscopy, Electron; D009437:Neuralgia / Q000276:immunology / Q000473:pathology*; D059225:Nociception; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D066148:Spinal Cord Dorsal Horn / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D013133:Spinothalamic Tracts / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D013601:T-Lymphocytes