Serum Metabolomics in the Rat Model of Recurrent Pelvic Pain

This study aimed to investigate systemic metabolic alterations underlying pain-depression comorbidity in the Recurrent Pelvic Pain (RPP) rat model using untargeted serum metabolomics (UPLC-Q-Orbitrap-MS). Comparative analysis revealed distinct metabolic profiles, identifying 234 differential metabolites enriched in steroids, fatty acyls, and carboxylic acids. KEGG analysis highlighted reprogramming of amino acid metabolism (e.g., phenylalanine, tyrosine, and tryptophan biosynthesis) and arachidonic acid metabolism. Integrative target prediction identified 10 key overlapping targets (e.g., TRPV1, OPRM1, PTGS2) associated with inflammatory response, fatty acid metabolism, and synaptic signaling. These targets were further linked to chronic pain and hyperalgesia. The metabolomic profile supports progressive nociceptive sensitization and reveals altered neurotransmitter biosynthesis pathways, providing insight into mechanisms of pain-depression comorbidity and potential therapeutic targets.