Background/Objectives: Ketamine offers effective pain relief with fewer side effects than traditional analgesics, making it a promising alternative for acute pain treatment. However, further research is needed to fully assess its role in perioperative care. This umbrella review aimed to compile the highest-quality evidence available regarding the application of ketamine in managing acute pain. Methods: A thorough search of the literature was carried out in PubMed, Scopus, and the Cochrane Library, including systematic reviews that focused on the application of ketamine in managing acute pain. The data extraction included the research type, analgesics used, number of studies and patients per review, pain types, scoring methods, ketamine doses, administration routes, and reporting guidelines. Results: Of the 807 records identified, 20 studies met the inclusion criteria. In accordance with the AMSTAR-2 evaluation, most of the systematic reviews were rated as critically low quality. Intravenous ketamine administered during the perioperative period was found to reduce the pain intensity of acute pain within 15–30 and 60 min following treatment, and decrease postoperative opioid consumption by 14–50% at both 24 and 48 h after surgery. Conclusions: Evidence shows that intravenous ketamine reduces the pain intensity, postoperative opioid use, and the risk of vomiting and nausea while improving analgesia, making it a valuable adjunct in perioperative pain management.

Background/Objectives: Pain and pain-related conditions are considered a global health and financial burden. In order to improve pain management, pain intensity assessment, and pain diagnosis, various biomarkers have been proposed. Since their clinical utility is not proven yet, the aim of this umbrella review is to synthesize existing evidence of all types of pain biomarkers available. Methods: Systematic searches were conducted in PubMed, Scopus, and the Cochrane Library from inception to 2 June 2025. Eligible studies were systematic reviews and meta-analyses examining any clinical, biochemical, genetic, neurophysiological, or imaging biomarker related to pain. The screening of studies, data extraction, and assessment of methodological quality using the AMSTAR-2 tool were conducted by two independent reviewers. Findings were summarized narratively. Results: A total of 49 systematic reviews and meta-analyses were included. Most reviews were rated as low or critically low quality. Inflammatory biomarkers (CRP, IL-6, TNF-α) reported the most consistent associations with chronic musculoskeletal pain, while neuroimaging and EEG measures reflected central nervous system alterations. Proteomic multi-protein panels demonstrated exploratory diagnostic potential, particularly for fibromyalgia, but lacked clinical validation. Evidence for genetic, hormonal, metabolic, neurochemical, and tissue-specific biomarkers was inconsistent and methodologically limited, supporting mechanistic rather than clinical inference. Conclusions: No single biomarker has achieved clinical validation for chronic pain, but several biomarker classes show promise. Future implications include high-quality longitudinal studies, standardized protocols, and multidimensional biomarker panels.