Chronic pain can be understood as an emergent property of a complex biopsychosocial system, where physiology, neuroscience, psychology, learning, and epigenetics interact with changing socioenvironmental conditions. This complexity may explain why current treatments often fail. Therapies that are both disruptive and adaptive at higher system levels, such as psychedelic-assisted therapies and mindfulness-based approaches, may offer benefits. Both have transdiagnostic value by disrupting rigid cognitive, emotional, and behavioral patterns and promoting neuroplasticity. Psychedelic therapies may hold unique promise for managing chronic pain.
Ketamine, an anesthetic added to the World Health Organization's essential medicines lists, is effective for acute pain at sub-anesthetic doses and may relieve some chronic pain. In 2019, its S-enantiomer was approved for treatment-resistant major depressive disorder. Pre-existing anxiety or depression and severe postoperative pain are risk factors for chronic postsurgical pain. This review examines ketamine's effects on biological and psychological processes underlying pain and mood disorders, focusing on non-NMDA receptor mechanisms and human trial results, to assess whether short-term ketamine can prevent acute postsurgical pain from becoming chronic.