Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls

Nocturnal peripheral vasoconstriction predicts the frequency of severe acute pain episodes in children with sickle cell disease

“…In the course of a number of studies in humans using peripheral perfusion as a biomarker to understand the triggers of VOC, we have shown that cold, 8 mental stress, 5 respiration, 7 and pain itself, 4,23 all factors mentioned by patients to precede VOC, cause significant peripheral vasoconstriction, and that each study participant, both SCD and controls, seems to have a characteristic baseline vasoconstriction pattern that was observed over several experimental visits 6 . We suspected that individuals with high inherent vasoconstriction would have more frequent VOC 2 .…”

“…While much of the literature in SCD has focused on nitric oxide (NO)‐mediated vascular dysfunction and cellular adhesion in the post‐capillary venules as key factors that may decrease microvascular flow and promote vaso‐occlusion, the role played by the sympathetic and parasympathetic nervous systems in causing vasoconstriction in the pre‐capillary arteriole, and decreasing microvascular flow has only recently been considered 3 . Our prior work has demonstrated that anticipatory pain, 4 experimental mental stress, 5 and cold exposure 6 all cause significant global vasoconstriction in SCD and non‐SCD controls and these responses vary significantly among all individuals 3 . Sighs (deep breaths) trigger peripheral vasoconstriction frequently in SCD but rarely in non‐SCD indivuals, 7 and cold face stimulation reduces the sensitivity of the baroreflex control of peripheral vascular resistance more in non‐transfused than transfused individuals with SCD or in controls 8 .…”

Spatiotemporal Alterations in Gait in Humanized Transgenic Sickle Mice

“…Vasoconstriction (or decrease in microvascular perfusion) is influenced greatly in response to anticipation of thermal pain in human sickle patients (57), and degree and rate of such neurally mediated-vasoconstriction is correlated with anxiety scores (51). While mental stress causes vasoconstriction in both sickle and healthy individuals (58), such vascular response may increase transit time of sickled RBCs and contribute to entrapment in microvasculature resulting in acute VOC. Additionally, neuroimaging analysis revealed that resting state functional connectivity is intensified in the locus coeruleus of the brain stems of SCD subjects compared to non-SCD anemic controls-indicating possibility of hyperactive sympathetic neurons contributing to modulation in peripheral microvascular blood flow (58).…”

“…While mental stress causes vasoconstriction in both sickle and healthy individuals ( 58 ), such vascular response may increase transit time of sickled RBCs and contribute to entrapment in microvasculature resulting in acute VOC. Additionally, neuroimaging analysis revealed that resting state functional connectivity is intensified in the locus coeruleus of the brain stems of SCD subjects compared to non-SCD anemic controls—indicating possibility of hyperactive sympathetic neurons contributing to modulation in peripheral microvascular blood flow ( 58 ). In patients with type1 and type2 diabetes (compared to healthy controls) decreased walking speed, more frequent stops and altered joint gait during movement were observed, while these patients also demonstrated 50% impairment in local tissue blood flow and other autonomic functions (vs. controls) ( 58 ).…”

“…Additionally, neuroimaging analysis revealed that resting state functional connectivity is intensified in the locus coeruleus of the brain stems of SCD subjects compared to non-SCD anemic controls—indicating possibility of hyperactive sympathetic neurons contributing to modulation in peripheral microvascular blood flow ( 58 ). In patients with type1 and type2 diabetes (compared to healthy controls) decreased walking speed, more frequent stops and altered joint gait during movement were observed, while these patients also demonstrated 50% impairment in local tissue blood flow and other autonomic functions (vs. controls) ( 58 ). Thus, it is possible that gait alteration in sickle mice is both a function of existing pain and its effect on the sympathetic nervous system.…”