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These findings suggest that, when evaluating the effects of amino acid-related metabolic axes, such as Gln-KG, on macrophage polarization, the key is not to simply classify them as pro-inflammatory or anti-inflammatory, but rather to focus on their integrated effects on anaplerotic flux, the spectrum of signaling metabolites, and the supply of epigenetic substrates, thereby reshaping inflammatory thresholds and reparative capacity across different timescales ( Nutrient-sensing pathways provide important clues for explaining the discrepant findings among different studies

This model is especially common in chronic pain management, where medications are often used repeatedly over time without correcting the underlying cause