A Stress and Pain Self-management m-Health App for Adult Outpatients with Sickle Cell Disease

项目摘要/摘要 针对PA-18-591-NOT-AG-20-034，我们的长期目标是了解 未识别的血管认知损害(VCI)/痴呆症对患有镰状细胞的成年人的痛觉影响 疾病(SCD)，转介到mHealth疼痛干预研究(1R01NR018848-01A1)。最典型的 SCD患者永久性神经损害的原因是无症状脑梗塞，它发生在 大约39%的18岁以下的儿童1和超过50%的30岁的成年人1血管损伤 可以通过影响上行和下行伤害性感受通路直接改变痛觉的处理 并通过影响认知和情感通路间接改变疼痛的处理。 对于SCD，VCI/痴呆症对疼痛报告的影响几乎是未知的，因为研究很少包括 综合神经认知测试或评估血管性痴呆风险的生物标志物指标 闭塞相关的无症状性脑梗塞和中风，如结合珠蛋白。结合珠蛋白基因(HP1-1， HP2-1或HP2-2)导致蛋白质具有不同的结构，从而产生不同的防御能力 清除细胞外毒性血红蛋白(Hb)。了解生物标记物指标/遗传基础 可能改变疼痛感知的VCI/痴呆对于推动患者的个性化治疗是相关的， 包括患有SCD、阿尔茨海默病或阿尔茨海默病相关痴呆(AD/ADRD)的人。在90年里 这项行政补充资料的具体目的是 TO：目标1：比较HP2-2和HP2-2携带者与VCI/痴呆(神经认知状态)的比例 HP2-1或HP1-1携带者。目标2：比较(A)感觉性疼痛知觉(强度、质量、神经病变 疼痛)和(B)HP2-2基因型和HP2-1或HP1-1的促炎分子浓度 基因分型。我们预计，超过一半的样本将患有以前未检测到的VCI/痴呆症和 携带HP2-2基因的患者患VCI/痴呆的比例高于携带HP2-1基因的患者 或HP1-1基因。我们还预计，感染HP2-2的患者将有更严重的疼痛和更多的亲和力。 炎症分子与HP2-1或HP1-1患者相比。这些初步数据将导致 NIH-R01专注于测试假设，患有VCI/痴呆的HP2-2 SCD患者将 与HP2-1或HP1-1患者相比，疼痛更严重，促炎分子更多。未来的研究将 旨在梳理出结合珠蛋白基因的贡献及其对促氧化和促氧化的调节。 成人SCD和疼痛门诊患者VIC/痴呆患者中游离血红蛋白的炎症特性。其他 研究将旨在测试输注正确的Hp血型(或异构体)对缓解Hp感染的效果 许多，如果不是全部，由游离血红蛋白和镰状细胞介导的毒性。我们的发现的影响将是 巨大，因为它们可以外推到目前影响5000万人的AD/ADRD患者 全世界的个人，每年有1000万新确诊病例。

Project Summary/Abstract In response to PA-18-591-NOT-AG-20-034, our long-term goal is to understand the potential influence of unrecognized vascular cognitive impairment (VCI)/dementia on pain perception among adults with sickle cell disease (SCD) who are referred to a mHealth pain intervention study (1R01NR018848-01A1). The most typical reason for permanent neurological damage in patients with SCD is silent cerebral infarct, which occurs in approximately 39% of children by 18 years1 of age and over 50% of adults by 30 years of age.1 Vascular injury to the brain can directly modify pain processing by affecting ascending and descending nociceptive pathways2 and indirectly modify pain processing by affecting cognitive and emotional pathways.2 However, in patients with SCD, the effect of VCI/dementia on pain reports are virtually unknown because studies rarely include comprehensive neurocognitive testing or assessment of biomarker indicators of risk for dementia from vaso- occlusion-related silent cerebral infarcts and stroke, such as haptoglobin. The haptoglobin genotype (Hp1-1, Hp2-1, or Hp2-2) results in proteins with different structures, resulting in a differential ability to protect against and clear extracellular toxic hemoglobin (Hb). Understanding the biomarker indicators/genetic basis for VCI/dementia that may alter pain perceptions is pertinent for driving personalized therapies for patients, including those with SCD, Alzheimer's disease, or Alzheimer's disease-related dementia (AD/ADRD). In 90 adults with SCD who are referred to the m-Health study, the specific aims of this administrative supplement are to: Aim 1: Compare the proportion with VCI/dementia (neurocognitive status) among patients with Hp2-2 and patients with HP2-1 or Hp1-1. Aim 2: Compare (a) sensory pain perception (intensity, quality, neuropathic pain) and (b) concentrations of proinflammatory molecules among Hp2-2 genotype and Hp2-1 or Hp1-1 genotypes. We expect that more than half of the sample will have previously undetected VCI/dementia and that a larger proportion of patients with the Hp2-2 genotype will have VCI/dementia than those with the HP2-1 or Hp1-1 genotype. We also expect that the patients with HP2-2 will have worse pain and more pro- inflammatory molecules as compared to patients with HP2-1 or Hp1-1. These preliminary data will lead to an NIH-R01 focused on testing the hypothesis that Hp2-2 patients with SCD who have VCI/dementia will have worse pain and more pro-inflammatory molecules as compared to HP2-1 or Hp1-1 patients. Future studies will be designed to tease out the contributions of haptoglobin genotype and its regulation of pro-oxidative and pro- inflammatory properties of free hemoglobin to VIC/dementia in adult outpatients with SCD and pain. Other studies will be designed to test effects of transfusing the right Hp-typed blood (or isoform) on mitigation of many, if not all, the toxicity mediated by free hemoglobin and sickled cells. The impact of our findings would be enormous because they could be extrapolated to patients with AD/ADRD that currently affects 50 million individuals worldwide, with 10 million new cases diagnosed annually.3