Comprehensive Mechanisms and Non-Invasive Treatment for Complex Regional Pain Syndrome: A Narrative Review

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition characterized by an exaggerated response to an initial stimulus, accompanied by autonomic, sensory, motor, and sudomotor dysfunctions. Recognized as a systemic disorder, CRPS involves complex interactions among inflammatory, immunologic, neurogenic, genetic, and psychological factors. The primary mechanisms include peripheral and central sensitization, sympathetic nervous system dysregulation, and altered somatosensory processing. However, the exact pathophysiology remains unclear, contributing to ongoing debate about optimal treatment approaches. Management typically involves a multimodal approach. Pharmacologic options such as corticosteroids, ketamine, and bisphosphonates have demonstrated relative safety and efficacy in clinical practice. Moreover, rehabilitation therapies -including cortically directed sensorimotor rehabilitation, range-of-motion or aerobic exercises, exposure therapy, transcutaneous electrical nerve stimulation, and thermal therapy -serve as valuable nonpharmacologic interventions. No consensus currently exists on standardized treatment protocols for CRPS, particularly regarding the choice of non-invasive approaches. In this context, a comprehensive understanding of the underlying pathophysiological mechanisms is essential for guiding appropriate management strategies. This review provides updated insights into the pathophysiological mechanisms of the disease, alongside a synthesis of evidence-based non-invasive treatment, to support mechanism-driven clinical decision-making, potentially improving treatment outcomes.