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

Cell Rep. 2018 Jan 30;22(5):1301-1312. doi: 10.1016/j.celrep.2018.01.006.


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.

Keywords: T cells; TrpV1; WCGNA; cold allodynia; gene expression; immune system; macrophages; neuropathic pain; tactile allodynia; transcript profiling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • Cold Temperature
  • Hyperalgesia / etiology
  • Hyperalgesia / immunology
  • Hyperalgesia / physiopathology*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuralgia / complications
  • Neuralgia / immunology
  • Neuralgia / physiopathology*
  • Sensory Receptor Cells / metabolism
  • T-Lymphocytes / immunology
  • TRPV Cation Channels / deficiency
  • Touch
  • Transcriptome*


  • TRPV Cation Channels
  • TRPV1 protein, mouse