A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: a replicated, randomized controlled clinical trial

Anna M Wahl,1 Daniel Bidstrup,1 Isabel G Smidt-Nielsen,1 Mads U Werner,2 Ole Hyldegaard,1,3 Per Rotbøll-Nielsen21Hyperbaric Unit, Department of Anesthesia, Head and Orthopedic Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark; 2Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark; 3Institute of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkPurpose: Animal studies have demonstrated anti-inflammatory, and anti-nociceptive properties of hyperbaric oxygen therapy (HBOT). However, physiological data are scarce in humans. In a recent experimental study, the authors used the burn injury (BI) model observing a decrease in secondary hyperalgesia areas (SHA) in the HBOT-group compared to a control-group. Surprisingly, a long-lasting neuroplasticity effect mitigating the BI-induced SHA-response was seen in the HBOT-preconditioned group. The objective of the present study, therefore, was to confirm our previous findings using an examiner-blinded, block-randomized, controlled, crossover study design.Patients and methods: Nineteen healthy subjects attended two BI-sessions with an inter-session interval of ≥28days. The BIs were induced on the lower legs by a contact thermode (12.5cm,2 47C°, 420s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O2, 90min) or ambient conditions ([AC]; 1 ATA, 21% O2), dividing cohorts equally into two sequence allocations: HBOT-AC or AC-HBOT. All sensory assessments performed during baseline, BI, and post-intervention phases were at homologous time points irrespective of sequence allocation. The primary outcome was SHA, comparing interventions and sequence allocations.Results: Data are mean (95% CI). During HBOT-sessions a mitigating effect on SHA was demonstrated compared to AC-sessions, ie, 18.8 (10.5–27.0) cm2 vs 32.0 (20.1–43.9) cm2 (P=0.021), respectively. In subjects allocated to the sequence AC-HBOT a significantly larger mean difference in SHA in the AC-session vs the HBOT-session was seen 25.0 (5.4–44.7) cm2 (P=0.019). In subjects allocated to the reverse sequence, HBOT-AC, no difference in SHA between sessions was observed (P=0.55), confirming a preconditioning, long-lasting (≥28days) effect of HBOT.Conclusion: Our data demonstrate that a single HBOT-session compared to control is associated with both acute and long-lasting mitigating effects on BI-induced SHA, confirming central anti-inflammatory, neuroplasticity effects of hyperbaric oxygen therapy.Keywords: burns, hyperbaric oxygenation, inflammation, pathophysiology, secondary hyperalgesia &nbsp