ArticlePLoS biology2021
Optogenetic activation of spinal microglia triggers chronic pain in mice.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Microglia respond to and induce anxiety and grooming in mice using calcium signaling.Molecular psychiatry · 2026Article
- Loss of SHP1 in Spinal Astrocytes Triggers T-Lymphocyte Infiltration and Nociceptive Hypersensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neuromodulation strategies in postburn care for pain rehabilitation and scar remodelling.Communications medicine · 2026Review
- Review
- Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Microglia-mediated BLA glutamatergic neuronal hyperactivity in the BLA-ACC pathway contributes to stress-induced visceral hypersensitivity and anxiety in rats.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- Beyond inflammation: a comprehensive microglial regulation model in chronic pain.Molecular biology reports · 2025Review
- Sex-Related Differences in Chronic Pain: A Narrative Review by a Multidisciplinary Task Force.Medicina (Kaunas, Lithuania) · 2025Review
- Optogenetic activation of cortical microglia promotes neuronal activity and pain hypersensitivity.Cell reports · 2025Article
- Neural ensembles that encode nocifensive mechanical and heat pain in mouse spinal cord.Nature neuroscience · 2025Article
- How microglia contribute to the induction and maintenance of neuropathic pain.Nature reviews. Neuroscience · 2025Review
- Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization.Science advances · 2025Article
- Article
- Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice.Acta pharmaceutica Sinica. B · 2024Article
- Gene therapy for chronic pain management.Cell reports. Medicine · 2024Review
- Optogenetics in oral and craniofacial research.Journal of Zhejiang University. Science. B · 2024Review
- Optogenetic stimulation of mouse Hoxb8 microglia in specific regions of the brain induces anxiety, grooming, or both.Molecular psychiatry · 2024Article
- Immune drivers of physiological and pathological pain.The Journal of experimental medicine · 2024Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity in both male and female mice. In addition, activation of microglial ReaChR up-regulated neuronal c-Fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased interleukin (IL)-1β production, which is likely mediated by inflammasome activation and calcium elevation. IL-1 receptor antagonist (IL-1ra) was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation. Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.