PRINCIPLES OF HYPERBARIC OXYGEN THERAPY IN COMPLEX REGIONAL PAIN SYNDROME: A SYSTEMATIC REVIEW

S. Sorrenti¹, M. Ciuffreda¹, E. Pisello¹, C. Pellegrino², A. Monacelli², G. Cucè³, G. Di Serafino⁴, C. Piangatelli¹, D. Galante⁵ | ¹U.O.C. Anestesia Rianimazione Terapia del Dolore, AST Ancona, Fabriano (AN), Italy; ²Scuola di Specializzazione in Anestesia Rianimazione, Terapia Intensiva e del Dolore, Università Politecnica delle Marche, Ancona, Italy; ³Scuola di Specializzazione in Igiene e Medicina Preventiva, Università degli Studi di Messina, Italy; ⁴U.O.C. Terapia del Dolore e Cure Palliative, AST Macerata; ⁵U.O.C. Anestesia e Rianimazione, ASL Foggia, Cerignola (FG), Italy

Introduction. Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder classified into Type I, without identifiable nerve injury, and Type II, associated with confirmed peripheral nerve damage (1). It predominantly affects women and most frequently involves the upper limbs. Diagnosis is based on the Budapest criteria. Increasing evidence suggests that inflammation, oxidative stress, tissue hypoxia, autonomic dysfunction, and neuroplastic alterations contribute to disease pathophysiology, providing a rationale for hyperbaric oxygen therapy (HBOT) (2).
Methods. A systematic review was performed according to the PRISMA Statement. PubMed and Cochrane Library databases were searched for studies published up to December 31, 2025, investigating the biological rationale and clinical application of HBOT in patients with CRPS.
Results. The available literature suggests that HBOT may improve pain through several complementary mechanisms, including enhancement of neuroplasticity, reduction of oxidative stress and neuroinflammation, preservation of mitochondrial function, inhibition of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), increased anti-inflammatory cytokine production (IL-10), inhibition of NF-κB with activation of the Nrf2 pathway, and reduction of tissue edema. Experimental studies consistently support these mechanisms, whereas clinical studies report encouraging but heterogeneous outcomes due to limited sample sizes and methodological variability.
Conclusions. HBOT represents a promising adjunctive treatment for CRPS within a multidisciplinary and multimodal pain management strategy. Although preclinical evidence strongly supports its biological mechanisms, current clinical evidence remains insufficient to recommend its routine use beyond selected patients. Well-designed randomized controlled trials are needed to clarify its efficacy and identify the patients most likely to benefit.