ALBERT

Description: Introduction: Sickle cell disease (SCD), an inherited blood disorder, is characterized by episodes of painful vaso-occlusive crises (VOC). Peripheral vasoconstriction may contribute to VOC by prolonging the transit time of red blood cells through the microvasculature. We recently demonstrated that heat-induced pain produces stronger vasoconstriction in SCD subjects versus controls, suggesting abnormal autonomic regulation of regional blood flow in SCD. Thus, although pain is generally thought to be a consequence of VOC, it is possible that pain itself may trigger a cascade of events that leads to large-scale VOC by promoting regional peripheral vasoconstriction. Objective: To determine if the underlying functional mechanisms of the vasoconstriction response to heat-induced pain in SCD differ from normal controls. Experimental Protocols: 22 SCD and 23 control (healthy and sickle cell trait) subjects were recruited at Children's Hospital of Los Angeles. Quasi-periodic pulses of pain were delivered on the right forearm using TSA-II neuro analyzer heating thermode. Electrocardiogram, respiration, continuous blood pressure and photoplethysmogram (PPG) were recorded. Both blood pressure and PPG were measured on the ring finger and thumb on the contralateral hand. Reductions in PPG amplitude were taken to represent vasoconstriction. Analysis: A mathematical model was applied to the data to extract the key parameters relating the thermal (pain) pulses, blood pressure and respiration to vasoconstriction. The model enabled the vasoconstriction response to pain to be decomposed into: 1) a neurogenic component, measuring the direct effect of the thermal pain pulse on vasoconstriction; 2) a local vascular component, relating fluctuations in blood pressure, induced by pain, to vasoconstriction; 3) a neurogenic-vascular interaction component, reflecting the modulation of the vascular component by the pain stimulus; and 4) a respiratory coupling component. Results: The model predicted stronger vasoconstriction responses to heat pain in SCD than controls (p = 0.002), consistent with the previous results reported by Khaleel et al. (Blood 126 (23):67, 2015). The pattern of the neurogenic response in both groups was similar but stronger in SCD (Fig 1a). The time-course of the local vascular component was quite pronounced in SCD (Fig 1b) - increases in blood pressure promoted stronger and more rapid vasoconstriction in SCD relative to controls. The neurogenic-vascular interaction (not shown) caused further peripheral vasoconstriction in SCD, but tended to reduce vasoconstriction in controls. The respiratory contribution was small in both groups. Discussion & Conclusions: Heat-induced pain produces peripheral vasoconstriction via direct autonomic nervous system activation, as well as indirectly through the local vascular response to pain-triggered blood pressure fluctuations. The complex dynamics of the vasoconstriction response can only be understood by application of a mathematical model incorporating several relevant simultaneously measured and frequently sampled physiological signals. The stronger neurogenic response in SCD suggests elevated sympathetic activity compared to controls. The local vascular component in the SCD subjects exhibits a higher reactivity to increases in local blood pressure that promotes vasoconstriction, consistent with underlying endothelial dysfunction. The contribution of neurogenic-vascular interaction derived from the model likely represents the degree to which sympathetic overactivity leads to vascular dysfunction in SCD. These results suggest that dysautonomia and its interaction with peripheral vascular dysregulation participate in the genesis of vaso-occlusive crisis. Figure 1 (a) average neurogenic response (% change from baseline) to a heat pain pulse (20 °C, 10-sec long) in SCD (N = 22) and controls (N = 23); (b) average vascular response (% change from baseline) to a blood pressure pulse induced by pain (10 mmHg, 10-sec long) in SCD and controls. Figure 1. (a) average neurogenic response (% change from baseline) to a heat pain pulse (20 °C, 10-sec long) in SCD (N = 22) and controls (N = 23); (b) average vascular response (% change from baseline) to a blood pressure pulse induced by pain (10 mmHg, 10-sec long) in SCD and controls. Disclosures Wood: Biomed Informatics: Consultancy; AMAG: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Vifor: Consultancy; World Care Clinical: Consultancy; Celgene: Consultancy; Biomed Informatics: Consultancy; AMAG: Consultancy; Apopharma: Consultancy; Apopharma: Consultancy; World Care Clinical: Consultancy; Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy.

Description: Introduction: Vaso-occlusive pain crises are considered the "hallmark" of sickle cell disease (SCD). Persistent occurrence is thought to lead to changes in the peripheral and central nervous system, which can then in turn lead to changes in pain sensitivity. Imaging studies have shown that hypnotic analgesia can reduce activity in supraspinal areas of the "pain matrix." To date there are no published studies looking at the effectiveness of hypnosis in altering pain perception in patients with SCD. The purpose of this study was to investigate changes in peripheral blood flow in response to a 30-minute hypnosis intervention and its relationship to pain sensitivity. Methods: To assess the effectiveness of increasing vasodilation, a laboratory based, single session hypnosis protocol was administered to a sample of 14 SCD patients and 14 healthy controls. Continuous readings for SpO2, pulse rate and pulse waveform was monitored using a pulse oximetry transducer placed on the left thumb. Bio-behavioral pain measures were collected during a standardized pain protocol before and after a hypnosis session, performed by a trained therapist. The protocol consisted of assessing pain tolerance and threshold via a heat probe (˚C) for "pain task 1", preceded by an anticipation period. "Pain task 2" consisted of assessing pain intensity via the same heat probe (˚C) on a 1-100 visual analog scale (VAS), preceded by another anticipation period. Results: To investigate blood-flow responses to their respective baseline (baseline vs. hypnosis), all recorded signal following these two periods was normalized respectively. Independent sample t-tests between both normalized anticipation and pain responses periods revealed controls showed no response to hypnosis for anticipation period 1(t(23.42) = .184, p = .855, d = .072), but SCD patients showed a large increase in blood flow (t(16.99) = 4.189, p = .0006, d = 1.79). Neither controls (t(21.05) = .00, p = .994, d = .003) or SCD patients (t(19.99) =.718, p = .481, d = .305) showed an effect of hypnosis in response to pain task 1. Neither controls (t(23.96) = -.139, p = .890, d = -.05) or SCD patients (t(18.82) = 1.035, p = .313, d = .441) showed a response to anticipation period 2, but the effect size reveals that this may be due to a lack of power. Neither controls (t(16.52) = .258, p = .799, d = .101) or SCD patients (t(19.63) = p = .5375, d = .268) showed no changes in response to hypnosis for pain task 2. Independent sample t-tests revealed no significant difference in pain threshold (t(13) = 0.941, p = .364, d = .251) or tolerance (t(13) = 0.937, p = 0.366, d = 0.250) in SCD patients before and after hypnosis. Differences in pain ratings were marginal but showed a decrease with medium effect (t(13) = -1.5315, p = 0.150, d = 0.409). The same tests revealed significant decreases in controls for pain threshold (t(13) = 2.825, p = 0.01, d = .755), pain tolerance (t(13) = 2.482, p = 0.02, d = 0.664), and pain rating (t(13) = 2.950, p = 0.01, d = .789). Conclusion: Results revealed that hypnosis may be an effective treatment in helping manage vasoconstriction in SCD as a response to cognitive appraisals about pain, as well as reducing pain sensitivity. The data presented provide preliminary clinical evidence of the use of hypnosis as a treatment method to improve vasodilation in SCD patients and decreasing pain crises, thus increasing overall quality of life. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Sickle cell disease (SCD) is a genetic disorder characterized by sudden onset of painful vaso-occlusive episodes (VOC) which can be triggered by stress as reported by sickle cell patients. The exact mechanism of VOC origin is not well understood; however, it could result as a progression of microvascular blockade with rigid sickled red blood cells (RBC). Anything that decreases regional blood flow (RBF) will increase the transit time that it takes the RBC to escape the microvasculature before it gets rigid and entrapped, thus increasing the chances of vaso-occlusion that may progress to VOC. The RBF is controlled by the autonomic nervous system (ANS) which is modulated by stress, and as we have previously shown, SCD patients have augmented autonomic mediated vasoconstriction response (VCR) to sigh and pain. Our studies showed significant VCR when subjects were told they were about to experience pain, suggesting that VCR might be the physiologic link between common VOC triggers like stress and sickled RBC retention in the microvasculature. Objectives: To study the effect of mental stress on autonomic parameters peripheral blood flow (PBF) and heart rate variability (HRV) in SCD. Methods: 19 SCD and 16 control (healthy and sickle cell trait) subjects were studied. Two standard mental stress tasks with graded levels of difficulty (N-back test and Stroop test) were presented to subjects using E-prime (Psychological software). Subjects were also exposed to a novel pain anticipation task, previously shown to induce VCR. PBF was measured using photo-plethysmography (PPG) on the left thumb. Reduction in PPG amplitude indicates vasoconstriction. Cardiac beat-to-beat variability (R-to-R interval;RRI) was extracted from electrocardiogram. ANS balance was derived from the following spectral indices of the RRI: high frequency power (HFP) ≈ parasympathetic activity, low frequency power (LFP), and the low/high ratio (LFP/HFP) representing sympathovagal balance. Average changes in PBF and HRV from the baseline were taken as the responses to the mental tasks. Results: There was a significant decrease in mean PBF, RRI and HFP during all the mental stressors (N-back test, Stroop test and pain fear) compared to the baseline (p

Description: INTRODUCTION: Sickle cell disease is an inherited blood disorder characterized by vaso-occlusive crises (VOC). HbS in red blood cells (RBC) polymerizes rapidly after it releases oxygen to tissues, causing RBC to become rigid. Anything that decreases flow in the microvasculature increases the chance that this flexible-to-rigid transformation occurs causing the rigid blood cell to lodge in the microvasculature, therefore increasing the chance of vaso-occlusion and the risk of VOC. Although hypoxia and stress are known risk factors for crises, the exact mechanism that initiates VOC events is not well known. We have previously shown that transient hypoxia causes parasympathetic withdrawal and sighs cause vasoconstriction more frequently in SCD subjects than in normal controls. Pain is the hallmark of SCD and is a consequence of VOC but has not been considered as a possible trigger of vasoconstriction that may lead to VOC. OBJECTIVES: To determine if heat induced pain causes decrease in peripheral blood flow (PBF) in SCD. METHODS: 30 SCD and 30 control subjects (healthy and sickle cell traits) were recruited at Children's Hospital Los Angeles (CHLA). Quasi-periodic pulses of pain were induced on the right forearm using TSA-II neuro analyzer heating thermode. We implemented a technique using cross correlation analysis to detect changes in complex microvascular flow signals measured bilaterally on the hands, using laser-Doppler flowmeter (LDF), Peripheral Arterial Tonometer (PAT) and photo-plethysmography (PPG). We also measured the average drop from baseline in the microvascular flow during the heat pain. Data were analyzed using one- and two- sample Student t-test. RESULTS: Data on 53 subjects were analyzed. There was a significant correlation between heat pain pulses and PBF responses, as well as a significant drop in blood flow in all study participants (PPG signal, both p

Description: Acupuncture has been used to treat a variety of childhood problems; however, the efficacy and safety of pediatric acupuncture remains unclear. This article reviews the existing empirical literature relating to the use of acupuncture for medical conditions in children. A systematic search of the literature revealed that acupuncture has been used to treat five main conditions in children, including pain, nocturnal enuresis, postoperative nausea/vomiting, laryngospasm/stridor, and neurological disorders. Despite a number of methodological issues, including limited sample sizes, lack of randomization, and inappropriate control groups, it is concluded that acupuncture represents a promising intervention for a variety of pediatric health conditions. To further address the safety, effectiveness, and acceptability of acupuncture in children, large-scale randomized controlled trials are needed.