Marie Louise Sezerano, Emery Niyonkuru
Postoperative pain remains a persistent clinical challenge affecting more than 80% of surgical patients, driving prolonged hospitalization, delayed recovery, and progression to chronic postsurgical pain. Opioid-centered analgesia, despite its historical primacy, is constrained by dependence, tolerance, opioid-induced hyperalgesia, and a critical post-discharge prescribing gap in which prescribed quantities consistently exceed actual patient consumption, perpetuating avoidable harm without proportional improvement in outcomes. Enhanced Recovery After Surgery protocols emphasize multimodal, opioid-sparing strategies combining pharmacologic agents including NSAIDs, acetaminophen, gabapentinoids, ketamine, dexmedetomidine, and intravenous lidocaine with neuraxial and peripheral nerve blocks and non-pharmacologic interventions including cognitive-behavioral therapy, physical rehabilitation, acupuncture, and digital therapeutics. Current evidence identifies NSAIDs combined with dexamethasone or regional anesthesia as delivering the greatest opioid-sparing efficacy, while emerging precision-based approaches incorporating pharmacogenomic-guided prescribing, machine learning-based pain prediction, and wearable monitoring platforms offer transformative opportunities for individualized perioperative analgesic optimization. Significant gaps persist including heterogeneity in multimodal regimen combinations, inconsistent outcome measures, limited post-discharge standardization, and insufficient long-term data on chronic postsurgical pain prevention and functional recovery across diverse surgical populations. Future research must prioritize procedure-specific, standardized, and pharmacogenomically informed multimodal protocols integrating technological innovations to optimize recovery, minimize opioid-related risks, and ensure sustainable, patient-centered perioperative pain management.