Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain

Nat Commun. 2020 Jan 14;11(1):264. doi: 10.1038/s41467-019-13839-2.


Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication
  • Cell Proliferation / drug effects
  • Female
  • Ganglia, Spinal / immunology*
  • Hyperalgesia / immunology
  • Immunosuppressive Agents / pharmacology
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microglia / metabolism
  • Microglia / physiology
  • Neuralgia / immunology*
  • Peripheral Nerve Injuries / immunology
  • Pregnancy
  • Sensory Receptor Cells / metabolism
  • Sex Factors
  • Tacrolimus / analogs & derivatives
  • Tacrolimus / pharmacology


  • AP20187
  • CSF1 protein, mouse
  • Immunosuppressive Agents
  • Macrophage Colony-Stimulating Factor
  • Tacrolimus