ArticleThe Journal of clinical investigation2014
Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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Who cites it
120 citing papers in PubMed.
- Preemptive oxycodone is superior to equal dose of sufentanil to reduce visceral pain and inflammatory markers after surgery: a randomized controlled trail.BMC anesthesiology · 2019Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Minocycline inhibits somatic hyperalgesia induced by malocclusion through up-regulating spinal IL-10 expression in female rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation.Journal of biomedical science · 2026Article
- Astrocyte-Specific Upregulation of Tumor Necrosis Factor Receptor II Ameliorates Pathological Phenotypes in APPNeuroscience bulletin · 2026Article
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Homer1a inhibits caspase-6 signaling to attenuate inflammatory pain in the spinal dorsal horn.The Journal of international medical research · 2025Article
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- Quercetin targets the Ccl4-Ccr5 axis to relieve neuropathic pain after spinal cord injury.APL bioengineering · 2025Article
- 4E-BP1-dependent translation in microglia controls mechanical hypersensitivity in male and female mice.The Journal of clinical investigation · 2025Article
- Alleviation of Neurological Disorders by Targeting Neurodegenerative-Associated Enzymes: Natural and Synthetic Molecules.International journal of molecular sciences · 2025Review
- Mechanisms and Therapeutic Prospects of Microglia-Astrocyte Interactions in Neuropathic Pain Following Spinal Cord Injury.Molecular neurobiology · 2025Review
- Mapping the publication trends of synaptic plasticity in neuropathic pain: A bibliometric analysis.Journal of anesthesia and translational medicine · 2024Article
- Gene therapy for chronic pain management.Cell reports. Medicine · 2024Review
- NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation.Hepatology communications · 2024Article
- Peripheral gating of mechanosensation by glial diazepam binding inhibitor.The Journal of clinical investigation · 2024Article
- Endoplasmic reticular stress as an emerging therapeutic target for chronic pain: a narrative review.British journal of anaesthesia · 2024Review
- Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- Microglial Modulation of Synaptic Maturation, Activity, and Plasticity.Advances in neurobiology · 2024Review
- Single-cell analysis of dorsal root ganglia reveals metalloproteinase signaling in satellite glial cells and pain.Brain, behavior, and immunity · 2023Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contribution of microglia and CASP6 in modulating synaptic transmission and pain is unclear. Here, we found that CASP6 is expressed specifically in C-fiber axonal terminals in the superficial spinal cord dorsal horn. Animals exposed to intraplantar formalin or bradykinin injection exhibited CASP6 activation in the dorsal horn. Casp6-null mice had normal baseline pain, but impaired inflammatory pain responses. Furthermore, formalin-induced second-phase pain was suppressed by spinal injection of CASP6 inhibitor or CASP6-neutralizing antibody, as well as perisciatic nerve injection of CASP6 siRNA. Recombinant CASP6 (rCASP6) induced marked TNF-α release in microglial cultures, and most microglia within the spinal cord expressed Tnfa. Spinal injection of rCASP6 elicited TNF-α production and microglia-dependent pain hypersensitivity. Evaluation of excitatory postsynaptic currents (EPSCs) revealed that rCASP6 rapidly increased synaptic transmission in spinal cord slices via TNF-α release. Interestingly, the microglial inhibitor minocycline suppressed rCASP6 but not TNF-α-induced synaptic potentiation. Finally, rCASP6-activated microglial culture medium increased EPSCs in spinal cord slices via TNF-α. Together, these data suggest that CASP6 released from axonal terminals regulates microglial TNF-α secretion, synaptic plasticity, and inflammatory pain.
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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.