Gut microbial butyrate influences pain through interconnected neuroimmune signaling, enteric nervous system-mediated gut–brain communication, intestinal and blood–brain barrier regulation, and neuronal plasticity, but its effects are highly context dependent. This Review integrates preclinical and clinical evidence across nociceptive, neuropathic, nociplastic, and cancer pain. We discuss translational limitations and potential approaches to improve treatment precision through microbiome- and host-informed patient stratification, optimization of butyrate exposure, and targeted delivery.
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Fu et al. (2026) studied this question.
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