Kai Schommer

Alterations in endogenous pain modulation in endurance athletes: an experimental study using quantitative sensory testing and the cold-pressor task.

&NA; Athletes were significantly less sensitive to mechanical pain but showed higher sensitivity to vibration compared with normally active controls. Assessment of conditioned pain modulation suggests that the endogenous pain‐inhibitory system is less responsive in athletes. &NA; There is evidence for long‐term alterations in pain tolerance among athletes compared with normally active controls. However, scientific data on pain thresholds in this population are inconsistent, and the underlying mechanisms for the differences remain unclear. Therefore, we assessed differences and similarities in pain perception and conditioned pain modulation (CPM) at rest in endurance athletes and normally active controls. The standardised quantitative sensory testing protocol (QST) of the ‘German‐Research‐Network‐on‐Neuropathic‐Pain’ was used to obtain comprehensive profiles on somatosensory functions. The protocol consisted of thermal and mechanical detection as well as pain thresholds, vibration thresholds, and pain sensitivity to sharp and blunt mechanical stimuli. CPM (the diffuse‐noxious‐inhibitory‐control‐like effect) was measured using 2 tonic heat pain test stimuli (at the temperature exceeding a subjective pain rating of 50/100) separated by a 2‐min cold‐pressor task (CPM‐TASK; conditioning stimulus). Pain ratings were measured with a numerical rating scale. Endurance capacity was validated by assessment of maximum oxygen uptake (VO2max). Participants included 25 pain‐free male endurance athletes (VO2max > 60 mL/min * kg) and 26 pain‐free normally active controls (VO2max < 45 mL/min * kg) matched based on age and body mass index. Athletes were significantly less sensitive to mechanical pain but showed higher sensitivity to vibration (P < 0.05). In athletes, CPM was significantly less activated by the conditioning stimuli (P < 0.05) when compared with normally active controls. Our data show that somatosensory processing in athletes differs in comparison with controls, and suggest that the endogenous pain inhibitory system may be less responsive. This finding may explain the paradoxical propensity of athletes to develop chronic widespread pain.

A measurement setup for direct 17O MRI at 7 T

An efficient breathing system was designed for direct 17O MRI to perform oxygen metabolism studies of the human brain. The breathing system consists of a demand oxygen delivery device for 17O2 supply and a custom‐built re‐breathing circuit with pneumatic switching valve. To efficiently deliver the 17O gas to the alveoli of the lungs, the system applies short gas pulses upon an inspiration trigger via a nasal cannula. During and after 17O2 administration, the exhaled gas volumes are stored and filtered in the re‐breathing section to make the most efficient use of the rare 17O gas. In an inhalation experiment, 2.2 ± 0.1 L of 70%‐enriched 17O2 were administered to a healthy volunteer and direct 17O MRI was performed for a total imaging time of 38 min with a temporal resolution of 50 s per 3D data set. Mapping of the maximum signal increase was carried out showing regional variations of oxygen concentration of up to 30% over the natural abundance of 17O water. Magn Reson Med, 2011.

Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema

Objective: Based on recent findings of microhemorrhages (MHs) in the corpus callosum (CC) in 3 individuals after nonfatal high-altitude cerebral edema (HACE), we hypothesized that hemosiderin depositions in the brain after high-altitude exposure are specific for HACE and remain detectable over many years. Methods: This was a cross-sectional study involving 37 mountaineers in 4 groups: 10 had experienced HACE, 8 high-altitude pulmonary edema, 11 severe acute mountain sickness, and 8 had climbed to altitudes ≥6,962 m without developing any high-altitude illness. HACE was defined as ataxia necessitating assistance with walking and/or decreased consciousness. Within <1 to 38 months after the qualifying incident, MRI of the brain was performed using a 3-tesla scanner and high-resolution susceptibility-weighted magnetic resonance sequences for detection of hemosiderin depositions, which were quantified by a score. Results: Unequivocal MHs located in the splenium of the CC were found in 8 subjects and questionable MHs were found in 2 subjects 1 to 35 months after HACE. They were located outside the CC in 5 more severe cases. MHs remained unchanged in those reexamined after 12 to 50 months. A few unequivocal MHs in the splenium of the CC were found in one subject after severe acute mountain sickness, while one subject with high-altitude pulmonary edema and 2 of the extreme altitude climbers had questionable lesions. In all other subjects, MHs were unequivocally absent. Conclusions: MHs detectable by susceptibility-weighted MRI predominantly in the splenium of the CC are long-lasting footprints of HACE.

Comments on Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia.

112:1788-1794, 2012. ; J Appl Physiol Joshua C. Weavil, Peter Bartsch and Charles F. Nelatury Samuel Verges, Patrick Levy, Eric M. Snyder, Bruce D. Johnson, Jonathon L. Stickford, Y. Millet, Benjamin D. Levine, James H. Wessel III, Bernard Wuyam, Renaud Tamisier, MacInnis, Michael S. Koehle, Thomas Rupp, Marc Jubeau, Stephane Perrey, Guillaume Laymon, Jack A. Loeppky, Matiram Pun, Kai Schommer, Mary C. Vagula, Martin J. S. Chapman, Johnny Conkin, Hugo Nespoulet, Darren P. Casey, Bryan J. Taylor, Abigail Olivier Girard, Michael S. Koehle, Jordan A. Guenette, Samuel Verges, Robert F. normobaric hypoxia induces/does not induce different responses from Comments on Point:Counterpoint: Hypobaric hypoxia

Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness.

Background The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO2 or HR. Conclusions/Significance Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.

Training in Normobaric Hypoxia and Its Effects on Acute Mountain Sickness after Rapid Ascent to 4559 m

In a randomized, placebo-controlled, double-blind study, we tested a 4-week program in normobaric hypoxia that is commercially offered for the prevention of acute mountain sickness (AMS). Twenty-two male and 18 female healthy subjects [mean age 33 +/- 7 (SD) years] exercised 70 min, 3 x /week for 3 weeks on a bicycle ergometer at workloads of 60% VO2max either in normoxia (normoxia group, NG) or in normobaric hypoxia (hypoxia group, HG), corresponding to altitudes of 2500, 3000, and 3500 m during weeks 1, 2, and 3, respectively. Four passive exposures of 90 min in normoxia (NG) or hypoxia corresponding to 4500 m (HG) followed in week 4. Five days after the last session, subjects ascended within 24 h from sea level to 4559 m (one overnight stay at 3611 m) and stayed there for 24 h. AMS was defined as LL (Lake Louise score) > or =5 and AMS-C > or =0.70. The AMS incidence (70% in NG vs. 60% in HG, p = 0.74), LL scores (7.1 +/- 4.3 vs. 5.9 +/- 3.4, p = 0.34), and AMS-C scores (1.50 +/- 1.22 vs. 0.93 +/- 0.81, p = 0.25) at the study endpoint were not significantly different between the groups. However, the incidence of AMS at 3611 m (6% vs. 47%, p = 0.01) and the functional LL score at 4559 m were lower in HG. SpO2 at 3611 m, heart rate during ascents, and arterial blood gases at 4559 m were not different between groups. We conclude that the tested program does not reduce the incidence of AMS within a rapid ascent to 4559 m, but our data show that it prevents AMS at lower altitudes. Whether such a program would prevent AMS at higher altitudes, but with slower ascent, remains to be tested.

Exercise intensity typical of mountain climbing does not exacerbate acute mountain sickness in normobaric hypoxia

Physical exertion is thought to exacerbate acute mountain sickness (AMS). In this prospective, randomized, crossover trial, we investigated whether moderate exercise worsens AMS in normobaric hypoxia (12% oxygen, equivalent to 4,500 m). Sixteen subjects were exposed to altitude twice: once with exercise [3 × 45 min within the first 4 h on a bicycle ergometer at 50% of their altitude-specific maximal workload (maximal oxygen uptake)], and once without. AMS was evaluated by the Lake Louise score and the AMS-C score of the Environmental Symptom Questionnaire. There was no significant difference in AMS between the exposures with and without exercise, neither after 5, 8, nor 18 h (incidence: 64 and 43%; LLS: 6.5 ± 0.7 and 5.1 ± 0.8; AMS-C score: 1.2 ± 0.3 and 1.1 ± 0.3 for exercise vs. rest at 18 h; all P > 0.05). Exercise decreased capillary Po(2) (from 36 ± 1 Torr at rest to 31 ± 1 Torr), capillary arterial oxygen saturation (from 72% at rest to 67 ± 2%), and cerebral oxygen saturation (from 49 ± 2% at rest to 42 ± 1%, as assessed by near-infrared spectroscopy; P < 0.05), and increased ventilation (capillary Pco(2) 27 ± 1 Torr; P < 0.05). After exercise, the increase in ventilation persisted for several hours and was associated with similar levels of capillary and cerebral oxygenation at the exercise and rest day. We conclude that moderate exercise at ~50% maximal oxygen uptake does not increase AMS in normobaric hypoxia. These data do not exclude that considerably higher exercise intensities exacerbate AMS.

Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

Background This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.80±1.00 μm; mean change±95%CI). This change was inverted towards the inner four subfields (TRTinner = −1.89±0.97 μm) with significant reduction of TRT in the fovea (TRTfoveal = −6.62±0.90 μm) at altitude. BCVA revealed no significant difference compared to baseline (0.06±0.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = −1.12±0.68 dB). At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure.

Missing correlation of retinal vessel diameter with high-altitude headache

The most common altitude‐related symptom, high‐altitude headache (HAH), has recently been suggested to originate from restricted cerebral venous drainage in the presence of increased inflow caused by hypoxia. In support of this novel hypothesis, retinal venous distension was shown to correlate with the degree of HAH. We quantified for the first time retinal vessel diameter changes at 4559 m using infrared fundus images obtained from a state of the art Spectralis™ HRA+OCT with a semiautomatic VesselMap 1® software. High‐altitude exposure resulted in altered arterial and venous diameter changes at high altitude, however, independent of headache burden.

Remote ischemic preconditioning delays the onset of acute mountain sickness in normobaric hypoxia

Acute mountain sickness (AMS) is a neurological disorder occurring when ascending too fast, too high. Remote ischemic preconditioning (RIPC) is a noninvasive intervention protecting remote organs from subsequent hypoxic damage. We hypothesized that RIPC protects against AMS and that this effect is related to reduced oxidative stress. Fourteen subjects were exposed to 18 hours of normoxia (21% oxygen) and 18 h of normobaric hypoxia (12% oxygen, equivalent to 4500 m) on different days in a blinded, randomized order. RIPC consisted of four cycles of lower limb ischemia (5 min) and 5 min of reperfusion, and was performed immediately before the study room was entered. A control group was exposed to hypoxia (12% oxygen, n = 14) without RIPC. AMS was evaluated by the Lake Louise score (LLS) and the AMS‐C score of the Environmental Symptom Questionnaire. Plasma concentrations of ascorbate radicals, oxidized sulfhydryl (SH) groups, and electron paramagnetic resonance (EPR) signal intensity were measured as biomarkers of oxidative stress. RIPC reduced AMS scores (LLS: 1.9 ± 0.4 vs. 3.2 ± 0.5; AMS‐C score: 0.4 ± 0.1 vs. 0.8 ± 0.2), ascorbate radicals (27 ± 7 vs. 65 ± 18 nmol/L), oxidized SH groups (3.9 ± 1.4 vs. 14.3 ± 4.6 μmol/L), and EPR signal intensity (0.6 ± 0.2 vs. 1.5 ± 0.4 × 106) after 5 h in hypoxia (all P < 0.05). After 18 hours in hypoxia there was no difference in AMS and oxidative stress between RIPC and control. AMS and plasma markers of oxidative stress did not correlate. This study demonstrates that RIPC transiently reduces symptoms of AMS and that this effect is not associated with reduced plasma levels of reactive oxygen species.