• Alan D Kaye, Angela Nguyen, Jolie Boullion, Mary-Elizabeth F Blue, Dillion W Hopson Allen, Rucha A Kelkar, Aya Mouhaffel, Andrew T Ro, Shahab Ahmadzadeh, Sahar Shekoohi, and Christopher L Robinson.
• Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
• Curr Pain Headache Rep. 2025 Jan 4; 29 (1): 44.

Purpose Of ReviewComplex regional pain syndrome (CRPS) is a chronic condition characterized by disproportional pain typically affecting an extremity. Management of CRPS is centered around specific symptomatology, which tends to be a combination of autonomic dysfunction, nociceptive sensitization, chronic inflammation, and/or motor dysfunction. Targeting the autoimmune component of CRPS provides a way to both symptomatically treat as well as minimize progression of CRPS.Recent FindingsUnderstanding the physiology of CRPS and strategies for treating and targeting immunophysiology behind CRPS allows examination of the efficacy of such treatments. IL-1 receptor antagonism, glucocorticoid administration, IVIG infusion, and TNFα inhibitors are treatments that target the immune response and decrease inflammation, thereby reducing pain and enhancing function in patients with CRPS. IL-1 receptor antagonism is thought to inhibit the inflammatory effects of IL-1, a key player in the inflammatory process in CRPS. Glucocorticoids have anti-inflammatory properties and can reduce inflammation in affected tissues. IVIG infusion involves administering immunoglobulins, which may modulate the immune response and reduce autoimmunity in CRPS. TNFα inhibitors block the action of TNFα, a pro-inflammatory cytokine associated with CRPS development. These therapies are further discussed at the extent of mechanism of action as well as advantages and limitations of such therapies. The present investigation provides a detailed summary of the mechanism of action, advantages, and limitations of novel immunomodulatory therapies and recent studies and trials that investigated these therapies for CRPS. Future studies are warranted related to the role of immunomodulators in the treatment of CRPS.© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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