Narrative review supports regional anesthesia and targeted non-opioids for chronic post-surgical pain and opioid use

Chronic Post-Surgical Pain (CPSP) and Postoperative Chronic Opioid Use (COU) pose significant public health challenges. Anesthesiologists play a vital role in modulating acute pain during surgery and influencing its chronic trajectory. CPSP is defined as pain persisting for ≥3 months, localized to the surgical field or relevant nerve territory, and with other causes excluded. COU, a surrogate marker for prolonged utilization, is defined as prolonged utilization (≥10 prescriptions or ≥120 days’ supply) in the postsurgical year, excluding the initial 90 postoperative days. This mini-review synthesizes evidence on perioperative risk factors, mechanistic pathways, and anesthetic/analgesic interventions to influence the development of CPSP and COU. We performed a narrative literature review (February 2000–December 2025) across PubMed and Google Scholar, focusing on risk factors and mitigation strategies for CPSP and COU. Key search terms included “CPSP,” “COU,” “multimodal analgesia,” “neuroinflammation,” “epigenetic changes,” “TIVA,” and “precision medicine.” The search prioritized randomized controlled trials, systematic reviews, and key preclinical studies. Chronicity is highly predictable based on preoperative psychosocial factors (e.g., anxiety, catastrophizing) and phenotypic hyperalgesia. Key mechanisms include central sensitization, neuroinflammation, epigenetic molecular programming, and gut-brain axis disruption. Evidence supports regional anesthesia (e.g., neuroaxial/paravertebral blocks) for CPSP prevention in high-risk procedures and targeted systemic non-opioids to mitigate opioid consumption and chronicity. CPSP and COU require a precision medicine approach that accounts for individual variability. This necessitates thorough preoperative risk stratification and the implementation of targeted, mechanism-based perioperative analgesia to intercept the neurobiological programming underlying chronic pain and opioid dependence.