Personalized Postoperative Pain Management and Therapies Based on Pharmacogenomics

Postoperative pain management must account for differences in drug metabolism, pain phenotype, prior opioid exposure, psychosocial vulnerability, and cognitive function. This narrative review proposes a staged precision-medicine framework separating clinically actionable pharmacogenomics from heterogeneous risk modifiers and investigational adjuncts. The strongest actionable guidance concerns CYP2D6-guided codeine and tramadol prescribing. Other genetic markers require interpretation alongside procedure-specific pain, comorbidities, medication exposure, and patient preferences rather than use as deterministic prescribing rules. Dopamine-related pathways provide a mechanistic link between pain, reward, motivation, and attention. Parkinson disease illustrates dopamine-pain interactions but is not a direct model of postoperative pain. Reward Deficiency Syndrome, the Genetic Addiction Risk Severity/Score, and the Reward Deficiency Syndrome Questionnaire-29 are considered exploratory constructs rather than validated tools for postoperative prescribing. The Continuous Visual Attention Test may offer objective neurocognitive monitoring through reaction time, response variability, and error measures. These measures are not pain-specific and require interpretation in the context of anesthesia, opioids, sedatives, sleep disruption, mood, delirium, baseline cognition, and pain intensity. Prospective studies should determine whether integrating clinical assessment, established pharmacogenomic guidance, and investigational behavioral and neurocognitive measures improves pain outcomes, opioid requirements, adherence, functional recovery, and safety. The framework defines research priorities and implementation endpoints while preserving multimodal analgesia, opioid stewardship, and clinical judgment as the foundation of care.