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This study utilizes 2923 plasma proteins and chronic pain of 51\u00a0644 participants from UK Biobank and finds 474 proteins linked to chronic pain in six sites: head, neck or shoulder, back, stomach or abdominal, hip, and knee, with 11 proteins sharing across pain sites. The identified proteins are largely enriched in immune and metabolic pathways and highly expressed in tissues like lungs and small intestines. Phenome\u2010wide analysis highlights the significance of pain\u2010related proteome on diverse facets of human health, and in\u2010depth Mendelian randomization validates 10 proteins (CD302, RARRES2, TNFRSF1B, BTN2A1, TNFRSF9, COL18A1, TNF, CD74, TNFRSF4, and BTN2A1) as markers of chronic pain. Furthermore, protein sets capable of classifying pain patients and healthy participants, particularly performing best in hip pain (area under curve, AUC = 0.725), are identified. 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