Complex Regional Pain Syndrome: Diagnosis, Pathophysiology, and Treatment Approaches

Abstract

Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by significant sensory, motor, and autonomic dysfunction, often following trauma or nerve injury. Historically known as causalgia and reflex sympathetic dystrophy, CRPS manifests as severe, disproportionate pain, often accompanied by hyperalgesia, allodynia, trophic changes, and motor impairments. Classified into type I (without nerve injury) and type II (associated with nerve damage), CRPS exhibits a complex pathophysiology involving peripheral and central sensitization, neurogenic inflammation, maladaptive brain plasticity, and potential autoimmune and psychological influences. The diagnosis relies primarily on clinical evaluation using criteria such as the Budapest Criteria, supported by supplementary tests to exclude differential diagnoses. However, its overlapping features with other conditions complicate diagnostic accuracy. The management of CRPS necessitates a multidisciplinary approach combining physical therapy, psychological support, and pharmacotherapy. Physical therapies, including graded motor imagery and mirror therapy, are essential for preserving function and preventing complications. Pharmacological treatments target neuropathic pain and inflammatory components, utilizing agents such as gabapentinoids, corticosteroids, and bisphosphonates. In refractory cases, interventional modalities like spinal cord stimulation and dorsal root ganglia stimulation provide promising options, although their efficacy remains variable. Emerging therapies, such as immune-modulatory treatments and advanced neuromodulation techniques, reflect the ongoing pursuit of effective interventions. This review synthesizes current knowledge, providing insights into diagnostic frameworks, pathophysiological mechanisms, and evolving treatment strategies to improve outcomes for individuals affected by CRPS.

Keywords: central sensitization; complex regional pain syndrome (crps); neuropathic pain; peripheral sensitization; spinal cord stimulation.