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Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.

Authors
  • Cobos, Enrique J1
  • Nickerson, Chelsea A2
  • Gao, Fuying3
  • Chandran, Vijayendran4
  • Bravo-Caparrós, Inmaculada5
  • González-Cano, Rafael2
  • Riva, Priscilla2
  • Andrews, Nick A2
  • Latremoliere, Alban2
  • Seehus, Corey R2
  • Perazzoli, Gloria6
  • Nieto, Francisco R7
  • Joller, Nicole8
  • Painter, Michio W2
  • Ma, Chi Him Eddie2
  • Omura, Takao2
  • Chesler, Elissa J9
  • Geschwind, Daniel H3
  • Coppola, Giovanni3
  • Rangachari, Manu10
  • And 2 more
  • 1 Kirby 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, Spain. , (Spain)
  • 2 Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • 3 Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 4 Department 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, USA.
  • 5 Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, Spain. , (Spain)
  • 6 Department 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, Spain. , (Spain)
  • 7 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, Spain. , (Spain)
  • 8 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • 9 The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
  • 10 Center 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, Canada. , (Canada)
  • 11 Kirby 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. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Jan 30, 2018
Volume
22
Issue
5
Pages
1301–1312
Identifiers
DOI: 10.1016/j.celrep.2018.01.006
PMID: 29386116
Source
Medline
Keywords
License
Unknown

Abstract

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.

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