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Altered Oxygenation, Vascular and Ischemic Pain Responses in Adults with Sickle Cell Anemia
source: American Society of Hematology
year: 2015
authors: Nathan S Fishman, Joseph Kim, Daniel Lichy, Kathleen Vaughan, Stephen Yoon, Niral Sheth, James Ahad, Deepika Darbari, Katherine Chadwick, Hans Ackerman, Alexander M. Gorbach, James G. Taylor
summary/abstract:The clinical hallmark of sickle cell anemia is the vaso-occlusive pain crisis. Although the exact cause for severe vaso-occlusive painful events is unknown, sickle cell microvasculature occlusion is thought to be the proximate cause producing tissue hypoxia, reperfusion injury and acute pain. Endothelial dysfunction is a prominent characteristic of sickle cell anemia, and it is unclear to what extent this abnormal vascular response contributes to vaso-occlusion and pain. We sought to evaluate the effects of hypoxia on sickle cell pain by performing a forearm ischemic pain test as a potential in vivomodel for vaso-occlusion. We hypothesized that sickle cell anemia patients would tolerate a shorter period of ischemia before reaching pain tolerance. We further hypothesized that sickle patients would show more hypoxia and increased vasodilation.
Thirty adults with sickle cell anemia were recruited and matched by age and sex to 30 normal volunteers. We first performed a timed ischemic pain test with brachial artery occlusion until subjects first reported pain (pain threshold) and until maximum pain tolerated (pain tolerance). Sickle cell subjects first reported pain at 411 vs. 589 s for normal volunteers (mean, p=0.07). Occlusion time to pain tolerance was significantly shorter for sickle cell patients (637 vs. 918 s, mean, p=0.004). Despite this difference, both groups reported nearly identical pain scores at threshold and tolerance. Stepwise linear regression for all subjects against 8 variables likely to influence pain showed sickle status (p=0.002) and gender (p=0.0008) were independently associated with time to tolerance, supporting our initial hypothesis.
Testing with continuous physiological monitoring was next repeated in sub-groups of 7 sickle cell and 9 normal subjects in an effort to understand the association between ischemia and pain progression. Before, during, and after brachial artery occlusion, oxygenated/deoxygenated hemoglobin concentration and tissue oxygen saturation were continuously monitored with near-infrared spectroscopy at the thenar eminence. We also recorded cutaneous blood flow with a Laser Speckle Contrast Imager (FLPI-2) in the volar aspect of forearm and continuous blood pressure and pulse in the contralateral arm. Monitoring was performed during steady state prior to occlusion (15 min), during occlusion until pain tolerance, and during recovery (20 min).
organization: National Heart, Lung and Blood Institute, Bethesda; National Institutes of Health, Bethesda; Children's National Medical Center / National Heart, Lung, and Blood Institute, Washington, DC.read more
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