Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 41, Issue 7, Pages 1096-1102Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b18-00278
Keywords
proliferation; microgliosis; spinal dorsal horn; neuropathic pain; peripheral nerve injury
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [JP15H02522, JP25117013]
- Core Research for Evolutional Science and Technology (CREST) program [JP17gm0910006]
- Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) [JP17ek0410034]
- Research Project on Elucidation of Chronic Pain
- Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research) [JP18am0101091]
- Japan Agency for Medical Research and Development
- Toray Science Foundation
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Neuropathic pain, a highly debilitating chronic pain following nerve damage, is a reflection of the aberrant functioning of a pathologically altered nervous system. Previous studies have implicated activated microglia in the spinal dorsal horn (SDH) as key cellular intermediaries in neuropathic pain. Microgliosis is among the dramatic cellular alterations that occur in the SDH in models of neuropathic pain established by peripheral nerve injury (PNI), but detailed characterization of SDH microgliosis has yet to be realized. In the present study, we performed a short-pulse labeling of proliferating cells with ethynyldeoxyuridine (EdU), a marker of the cell cycle S-phase, and found that EdU(+) microglia in the SDH were rarely observed 32 h after PNI, but rapidly increased to the peak level at 40 h post-PNI. Numerous EdU(+) microglia persisted for the next 20h (60h post-PNI) and decreased to the baseline on day 7. These results demonstrate a narrow time window for rapidly inducing a proliferation burst of SDH microglia after PNI, and these temporally restricted kinetics of microglial proliferation may help identify the molecule that causes microglial activation in the SDH, which is crucial for understanding and managing neuropathic pain.
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