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Updated: Jul 5, 2025
Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution
Lauren J Donovan1, Caldwell M Bridges1, Amy R Nippert1
1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA.
Abstract:
Microglia are implicated as primarily detrimental in pain models; however, they exist across a continuum of states that contribute to homeostasis or pathology depending on timing and context. To clarify the specific contribution of microglia to pain progression, we take advantage of a temporally controlled transgenic approach to transiently deplete microglia. Unexpectedly, we observe complete resolution of pain coinciding with microglial repopulation rather than depletion. We find that repopulated mouse spinal cord microglia are morphologically distinct from control microglia and exhibit a unique transcriptome. Repopulated microglia from males and females express overlapping networks of genes related to phagocytosis and response to stress. We intersect the identified mouse genes with a single-nuclei microglial dataset from human spinal cord to identify human-relevant genes that may ultimately promote pain resolution after injury. This work presents a comprehensive approach to gene discovery in pain and provides datasets for the development of future microglial-targeted therapeutics.
Insights
Transiently depleting microglia unexpectedly led to pain resolution upon their repopulation. Repopulated microglia exhibit distinct molecular profiles, offering new therapeutic targets for pain management.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Microglia, the immune cells of the central nervous system, are traditionally viewed as detrimental in pain.
- However, microglia exist in diverse states that can influence both homeostasis and pathology.
- Their precise role in pain progression requires further elucidation.
Purpose of the Study:
- To investigate the specific contribution of microglia to pain progression using a temporally controlled depletion model.
- To identify molecular signatures of microglia associated with pain resolution.
Main Methods:
- Utilized a temporally controlled transgenic approach for transient microglial depletion in a mouse pain model.
- Analyzed morphological and transcriptomic changes in repopulated microglia.
- Intersected mouse gene data with human single-nuclei microglial datasets.
Main Results:
- Complete pain resolution was observed coinciding with microglial repopulation, not depletion.
- Repopulated microglia displayed distinct morphology and transcriptomes compared to control microglia.
- Overlapping gene networks related to phagocytosis and stress response were identified in repopulated microglia from both sexes.
- Identified human-relevant genes associated with potential pain resolution.
Conclusions:
- Microglial repopulation, rather than depletion, can lead to pain resolution.
- Repopulated microglia possess unique molecular characteristics that may be key to pain relief.
- This study provides valuable datasets for developing novel microglial-targeted therapeutics for pain management.
