eLife (Jul 2015)
A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model
- Yasunobu Arima,
- Daisuke Kamimura,
- Toru Atsumi,
- Masaya Harada,
- Tadafumi Kawamoto,
- Naoki Nishikawa,
- Andrea Stofkova,
- Takuto Ohki,
- Kotaro Higuchi,
- Yuji Morimoto,
- Peter Wieghofer,
- Yuka Okada,
- Yuki Mori,
- Saburo Sakoda,
- Shizuya Saika,
- Yoshichika Yoshioka,
- Issei Komuro,
- Toshihide Yamashita,
- Toshio Hirano,
- Marco Prinz,
- Masaaki Murakami
Affiliations
- Yasunobu Arima
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Daisuke Kamimura
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Toru Atsumi
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Masaya Harada
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Tadafumi Kawamoto
- Department of Dentistry, Tsurumi University, Yokohama, Japan
- Naoki Nishikawa
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Department of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Andrea Stofkova
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Takuto Ohki
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Kotaro Higuchi
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Yuji Morimoto
- Department of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Peter Wieghofer
- Institute of Neuropathology, Faculty of Biology, University of Freiburg, Freiburg, Germany
- Yuka Okada
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
- Yuki Mori
- Laboratory of Biofunctional Imaging, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Saburo Sakoda
- Department of Neurology, National Hospital Organization Toneyama Hospital, Osaka, Japan
- Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan
- Yoshichika Yoshioka
- Laboratory of Biofunctional Imaging, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- Issei Komuro
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Toshihide Yamashita
- Laboratory of Molecular Neuroscience, Graduate School of Medicine, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
- Toshio Hirano
- Osaka University, Osaka, Japan
- Marco Prinz
- BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany
- Masaaki Murakami
- Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
- DOI
- https://doi.org/10.7554/eLife.08733
- Journal volume & issue
-
Vol. 4
Abstract
Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target.
Keywords
