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

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 RangachariClifford J. Woolf, Michael Costigan

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)1301-1312
Number of pages12
JournalCell Reports
Volume22
Issue number5
DOIs
StatePublished - Jan 30 2018
Externally publishedYes

Keywords

  • T cells
  • TrpV1
  • WCGNA
  • cold allodynia
  • gene expression
  • immune system
  • macrophages
  • neuropathic pain
  • tactile allodynia
  • transcript profiling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Cobos, E. J., Nickerson, C. A., Gao, F., Chandran, V., Bravo-Caparrós, I., González-Cano, R., Riva, P., Andrews, N. A., Latremoliere, A., Seehus, C. R., Perazzoli, G., Nieto, F. R., Joller, N., Painter, M. W., Ma, C. H. E., Omura, T., Chesler, E. J., Geschwind, D. H., Coppola, G., ... Costigan, M. (2018). Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling. Cell Reports, 22(5), 1301-1312. https://doi.org/10.1016/j.celrep.2018.01.006