Nox2-dependent signaling between macrophages and sensory neurons contributes to neuropathic pain hypersensitivity

Pain. 2014 Oct;155(10):2161-70. doi: 10.1016/j.pain.2014.08.013. Epub 2014 Aug 17.


Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve injury, Nox2-positive macrophages were recruited to DRG, and ROS production was increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor α was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain.

Keywords: Dorsal root ganglion; Knockout mice; Neuropathic pain; Peripheral nerve injury; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / physiology*
  • Ganglia, Spinal / metabolism
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism*
  • Macrophages / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism*
  • Neuralgia / etiology
  • Neuralgia / metabolism*
  • Peripheral Nerve Injuries / complications
  • Peripheral Nerve Injuries / metabolism
  • Reactive Oxygen Species / metabolism
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction / physiology


  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases