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Despite advances in understanding pain mechanisms, there remains a critical need for validated biomarkers to enhance diagnosis, prognostication, and personalized therapy. This review synthesizes recent advancements in identifying and validating acute and chronic pain biomarkers, including imaging, molecular, sensory, and neurophysiological approaches. We emphasize the emergence of composite, multimodal strategies that integrate psychosocial factors to improve the precision and applicability of biomarkers in chronic pain management. Neuroimaging techniques like MRI and positron emission tomography provide insights into structural and functional abnormalities related to pain, while electrophysiological methods like electroencepholography and magnetoencepholography assess dysfunctional processing in the pain neuroaxis. Molecular biomarkers, including cytokines, proteomics, and metabolites, offer diagnostic and prognostic potential, though extensive validation is needed. Integrating these biomarkers with psychosocial factors into clinical practice can revolutionize pain management by enabling personalized treatment strategies, improving patient outcomes, and potentially reducing healthcare costs. Future directions include the development of composite biomarker signatures, advances in arti\ufb01cial intelligence, and biomarker signature integration into clinical decision support systems. Rigorous validation and standardization efforts are also necessary to ensure these biomarkers are clinically useful. Large-scale collaborative research will be vital to driving progress in this \ufb01eld and implementing these biomarkers in clinical practice. This comprehensive review highlights the potential of biomarkers to transform acute and chronic pain management, offering hope for improved diagnosis, treatment personalization, and patient outcomes.<\/jats:p>","DOI":"10.1136\/rapm-2024-106030","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T08:20:20Z","timestamp":1738743620000},"page":"110-120","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Innovations in acute and chronic pain biomarkers: enhancing diagnosis and personalized therapy"],"prefix":"10.1136","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-5348","authenticated-orcid":false,"given":"Sean","family":"Mackey","sequence":"first","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Aghaeepour","sequence":"additional","affiliation":[{"name":"Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Gaudilliere","sequence":"additional","affiliation":[{"name":"Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chih","family":"Kao","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Kaptan","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Lannon","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Pfyffer","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Weber","sequence":"additional","affiliation":[{"name":"Division of Pain Medicine, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"2025101111443320000_50.2.110.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2016.06.009"},{"key":"2025101111443320000_50.2.110.2","unstructured":"In relieving pain in America: a blueprint for transforming prevention, care. 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