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

Xiaobing Yu (), Hongju Liu, Katherine A. Hamel, Maelig G. Morvan, Stephen Yu, Jacqueline Leff, Zhonghui Guan, Joao M. Braz and Allan I. Basbaum ()
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Xiaobing Yu: University of California San Francisco
Hongju Liu: University of California San Francisco
Katherine A. Hamel: University of California San Francisco
Maelig G. Morvan: University of California San Francisco
Stephen Yu: University of California San Francisco
Jacqueline Leff: University of California San Francisco
Zhonghui Guan: University of California San Francisco
Joao M. Braz: University of California San Francisco
Allan I. Basbaum: University of California San Francisco

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-13839-2

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