Background: Chronic pain is a major global health problem for which current treatments often provide insufficient relief. Tissue hypoxia and redox imbalance may contribute to its pathophysiology, prompting interest in hyperbaric oxygen therapy (HBOT) as a potential adjunctive treatment. This review evaluates the therapeutic effects of HBOT in adults with chronic pain syndromes. Methods: A PRISMA-guided systematic review was conducted (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials; January 2000 - August 2025). Randomized controlled trials (RCTs) evaluating HBOT in adults with chronic pain were included. Primary outcomes were pain measures (intensity, distribution and sensitivity). Secondary outcomes included multidimensional pain-related outcomes (quality of life, functioning and psychological well-being), analgesic use, neuroimaging findings, and adverse events. Risk of bias was assessed using the Cochrane RoB 2 tool. Due to study heterogeneity, results were synthesized narratively. Results: Eleven RCTs (480 participants) were included, predominantly involving fibromyalgia (n=8), with additional studies in complex regional pain syndrome (CRPS) (n=1), idiopathic trigeminal neuralgia (n=1) and radiation-induced brachial neuropathy (n=1). Sample sizes ranged from 17 to 71 participants. Most trials showed some concerns or high risk of bias, mainly due to subjective outcomes and lack of blinding. In fibromyalgia, HBOT showed consistent within-group improvements in pain, functioning, and quality of life, with some studies demonstrating between-group benefits. Limited evidence in CRPS and trigeminal neuralgia suggested possible benefit, whereas the trial in radiation-induced brachial plexopathy showed no meaningful improvement. HBOT was generally well tolerated, with mostly mild adverse events. Conclusion: HBOT shows potential as an adjunctive intervention for selected chronic pain syndromes, particularly fibromyalgia. However, condition-specific effects, inconsistent superiority over controls, methodological limitations, protocol heterogeneity, and limited long-term follow-up constrain the strength of evidence. Larger, standardized trials with extended follow-up are needed before routine clinical implementation can be recommended. Keywords: HBOT, chronic pain, functional outcomes, fibromyalgia, complex regional pain syndrome, trigeminal neuralgia
Leys et al. (Sun,) studied this question.