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Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation - PubMed

3 days ago
  • #chronic pain
  • #metabolite signaling
  • #neuroinflammation
  • Chronic pain involves neuronal hyperexcitability and neuroinflammation, with metabolites like lactate, succinate, and itaconate signaling to drive glial reprogramming and neuronal sensitization.
  • A metabolite-neuro-immune relay model describes how metabolic changes in astrocytes, microglia, and immune cells produce specific metabolite patterns, influencing glial states and resulting cytokines that remodel pain circuits.
  • Spatial and temporal aspects of metabolic signaling create self-reinforcing neuroimmune loops, offering therapeutic targets such as modulating glycolysis, blocking succinate receptors, or enhancing the IRG1-itaconate-NRF2 axis for chronic pain treatment.