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

Chronic pain is sustained by coupled neuronal hyperexcitability and neuroinflammation, yet prevailing frameworks incompletely explain why similar injuries diverge toward recovery or persistent sensitisation. Growing evidence indicates that lactate, succinate and itaconate act as signalling metabolites that shape glial state transitions and nociceptive circuit gain. Here, we synthesise preclinical and emerging clinical findings and propose a metabolite–neuro–immune relay model in which metabolic