Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
Summary: Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a mo...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718300068 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Enrique J. Cobos Chelsea A. Nickerson Fuying Gao Vijayendran Chandran Inmaculada Bravo-Caparrós Rafael González-Cano Priscilla Riva Nick A. Andrews Alban Latremoliere Corey R. Seehus Gloria Perazzoli Francisco R. Nieto Nicole Joller Michio W. Painter Chi Him Eddie Ma Takao Omura Elissa J. Chesler Daniel H. Geschwind Giovanni Coppola Manu Rangachari Clifford J. Woolf Michael Costigan |
| spellingShingle |
Enrique J. Cobos Chelsea A. Nickerson Fuying Gao Vijayendran Chandran Inmaculada Bravo-Caparrós Rafael González-Cano Priscilla Riva Nick A. Andrews Alban Latremoliere Corey R. Seehus Gloria Perazzoli Francisco R. Nieto Nicole Joller Michio W. Painter Chi Him Eddie Ma Takao Omura Elissa J. Chesler Daniel H. Geschwind Giovanni Coppola Manu Rangachari Clifford J. Woolf Michael Costigan Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling Cell Reports |
| author_facet |
Enrique J. Cobos Chelsea A. Nickerson Fuying Gao Vijayendran Chandran Inmaculada Bravo-Caparrós Rafael González-Cano Priscilla Riva Nick A. Andrews Alban Latremoliere Corey R. Seehus Gloria Perazzoli Francisco R. Nieto Nicole Joller Michio W. Painter Chi Him Eddie Ma Takao Omura Elissa J. Chesler Daniel H. Geschwind Giovanni Coppola Manu Rangachari Clifford J. Woolf Michael Costigan |
| author_sort |
Enrique J. Cobos |
| title |
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling |
| title_short |
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling |
| title_full |
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling |
| title_fullStr |
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling |
| title_full_unstemmed |
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling |
| title_sort |
mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-01-01 |
| description |
Summary: Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type. : Cobos et al. correlated gene expression with behavior after nerve injury and found that two distinct processes contribute to neuropathic pain: one that occurs in neurons, leading to cold allodynia, and another that includes immune cells and neurons, leading to tactile allodynia. Keywords: neuropathic pain, macrophages, T cells, immune system, TrpV1, tactile allodynia, cold allodynia, gene expression, transcript profiling, WCGNA |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718300068 |
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doaj-13a9fb8f80d74f569011eeba624c74542020-11-25T00:46:48ZengElsevierCell Reports2211-12472018-01-0122513011312Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression ProfilingEnrique J. Cobos0Chelsea A. Nickerson1Fuying Gao2Vijayendran Chandran3Inmaculada Bravo-Caparrós4Rafael González-Cano5Priscilla Riva6Nick A. Andrews7Alban Latremoliere8Corey R. Seehus9Gloria Perazzoli10Francisco R. Nieto11Nicole Joller12Michio W. Painter13Chi Him Eddie Ma14Takao Omura15Elissa J. Chesler16Daniel H. Geschwind17Giovanni Coppola18Manu Rangachari19Clifford J. Woolf20Michael Costigan21Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, Spain; Biosanitary Research Institute, University Hospital Complex of Granada, 18012 Granada, SpainKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, School of Medicine, University of Florida, Gainesville, FL 32610-0296, USADepartment of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, SpainKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USADepartment of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, Spain; Department of Anatomy and Embryology, School of Medicine, University of Granada, 18071 Granada, SpainDepartment of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, Spain; Biosanitary Research Institute, University Hospital Complex of Granada, 18012 Granada, SpainCenter for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USACenter for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosciences, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, CanadaKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USAKirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Anesthesia, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type. : Cobos et al. correlated gene expression with behavior after nerve injury and found that two distinct processes contribute to neuropathic pain: one that occurs in neurons, leading to cold allodynia, and another that includes immune cells and neurons, leading to tactile allodynia. Keywords: neuropathic pain, macrophages, T cells, immune system, TrpV1, tactile allodynia, cold allodynia, gene expression, transcript profiling, WCGNAhttp://www.sciencedirect.com/science/article/pii/S2211124718300068 |