Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

Rasmussen, Vibe Maria; Borgen, A. E.; Jansen, Erik C.; Nielsen, Per Hostrup; Werner, Mads U.

doi:10.1111/aas.12492

Cited by 16 publications

(37 citation statements)

References 74 publications

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“…Several experimental studies, using different methods and treatment dosages, have shown anti-inflammatory effects of HBOT,5–7 but there is a paucity of studies investigating these effects in humans. A previous study,8 carried out by the present authors, was the first in humans to demonstrate an ameliorating effect of HBOT on the pathophysiological consequences following a previously validated inflammatory burn injury (BI) model 9–11. We demonstrated an attenuation of secondary hyperalgesia areas (SHA) in normal skin surrounding the injury, likely reflecting a central anti-nociceptive effect.…”

Section: Introductionsupporting

confidence: 50%

“…The original study was a randomized, controlled, crossover study with an open therapeutic design 8. The objective of the present study was to replicate our findings, adding an improved single-blinded design, ie, blinding for examiner bias.…”

Section: Introductionmentioning

confidence: 68%

“…The HBOT procedure was performed as previously reported in detail 8. The procedure consisted of an initial compression period lasting 5 min (Figure 2A), reaching a plateau of 2.4 ATA during which HBOT was administered for 90 min (100% O 2 ) using no air-breaks, followed by a short decompression period (Figure 2A).…”

Section: Methodsmentioning

confidence: 99%

“…Assessments of pin-prick pain threshold (PPT) were made in the testing area using “weighted-pins” (8, 16, 32, 64, 128, 256 and 512 mN; MRC Systems, Heidelberg, Germany) according to a modified Dixon’s “up-and-down method”,18–20 as previously reported 8. The PPT was determined four times, and the median value was used in further analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Wahl¹,

Bidstrup²,

Smidt-Nielsen³

et al. 2019

JPR

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Purpose 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 ≥28 days. The BIs were induced on the lower legs by a contact thermode (12.5 cm 2 , 47C°, 420 s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O 2 , 90 min) or ambient conditions ([AC]; 1 ATA, 21% O 2 ), 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) cm 2 vs 32.0 (20.1–43.9) cm 2 ( 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) cm 2 ( 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 (≥28 days) 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.

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Section: Introductionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Wahl¹,

Bidstrup²,

Smidt-Nielsen³

et al. 2019

JPR

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“…The different characteristics of the punctate stimulators were chosen in order to get skin pressures just perceivable (just above detection threshold; PS1 ; Table 1), between detection and pain threshold ( PS2 ), near pain threshold ( PS3 ) and above pain threshold ( PS4 ), in hyperalgesic skin (Rasmussen et al, 2015; Ravn et al, 2013). The PS1–PS3 were polyamide monofilaments (Stoelting Europe, Dublin, Ireland; designated values 2.36, 4.93, 6.65; Table 1) while PS4 was a “weighted-pin” stimulator (MRC Systems, Heidelberg; 512 mN).…”

Section: Methodsmentioning

confidence: 99%

Demarcation of secondary hyperalgesia zones: Punctate stimulation pressure matters

Ringsted

Enghuus

Petersen

et al. 2015

Journal of Neuroscience Methods

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Background Secondary hyperalgesia is increased sensitivity in normal tissue near an injury, and it is a measure of central sensitization reflecting injury-related effects on the CNS. Secondary hyperalgesia areas (SHAs), usually assessed by polyamide monofilaments, are important outcomes in studies of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). New Method The study was a two-observer, test-retest study with the two sessions separated by 6 wks. An observer-blinded design adjusted to examine day-to-day and observer-to-observer variability in SHA was used. In 23 healthy volunteers (12 females/11 males) a BI was induced by a contact thermode (47.0°C, 420 s, 2.5 × 5.0 cm2). The SHA, demarcated by polyamide monofilaments (bending force: 0.2, 69 and 2,569 mN) and a “weighted-pin” stimulator (512 mN), were assessed 45 to 75 min after each BI. Results A random effect, linear mixed model demonstrated a logarithmic correlation between elicited skin pressures (mN/mm2) and the SHAs (P < 0.0001). No day-to-day or observer-to-observer differences in SHAs were observed. Intraclass correlation coefficients, in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability between observers. Comparison with existing methods No standardized approach in SHA-assessment has hitherto been presented. Conclusions This is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used.

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Human surrogate models of central sensitization: A critical review and practical guide

Quesada

Kostenko

et al. 2021

European Journal of Pain

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Background: As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock-like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission. Data treatment: We therefore performed a systematic literature review (PubMed-Medline, Cochrane, WoS, ClinicalTrials) and semi-quantitative meta-analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury. Results: From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low-or high-frequency electrical stimulation, thermode-induced heat-injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower.The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development. Conclusions: While there is no single "optimal" model of central sensitization, the range of validated and easy-to-use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data. Significance: Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogateThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

Cited by 16 publications

References 74 publications

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

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

Demarcation of secondary hyperalgesia zones: Punctate stimulation pressure matters

Human surrogate models of central sensitization: A critical review and practical guide

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