Analgesic technique on pain and biomarkers during sickle pain crisis

描述（由申请人提供）：尽管对患有镰状细胞病的儿童进行了广泛的研究，但对患有该疾病的成人的研究却很少。许多成年镰状细胞病（SCD）患者每天都会感到疼痛。虽然镰状细胞相关疼痛的病理生理是复杂的，但微循环闭塞与组织缺血和炎症级联反应的激活被认为是相关的。急性血管闭合性危象是镰状细胞相关就诊的主要原因。尽管有强有力的证据表明组织和血管炎症在急性血管闭塞性危象的发生和维持中起作用，但尚未发现与急性危象的强度或持续时间相关的特异性血清生物标志物。一种可以通过血清生物标志物评估并改善的有效镇痛治疗模式在SCD疼痛危象中尚未被系统地研究。因此，本R21提案的目的是验证镇痛质量和方法影响特定血液生物标志物水平并与疼痛水平相关的假设。因此，本研究将为了解镰状细胞危像对疼痛的治疗效果提供一个独特的机会，并为未来的干预和特定血清生物标志物的临床应用提供基础。第一个目的是验证疼痛技术模式影响疼痛危机结果的假设，疼痛危机由疼痛评分、镇痛药消耗和SCD疼痛危机的住院率决定。SCD受试者将在常规医院就诊期间登记（总目标为75名受试者），并在急性疼痛危机的紧急就诊期间随访。将使用标准的肠外和口服阿片类药物治疗的镇痛技术。目的是评估镇痛治疗对急性镰状疼痛危像期间和之后急性和亚急性疼痛水平的影响，确定血清炎症/疼痛分子作为SCD疼痛危像中疼痛严重程度的生物标志物，并检验血清生物标志物可用于预测SCD住院需求、止痛药需求增加以及可能的疾病并发症发生率的假设。此外，确定镇痛治疗是否影响血清生物标志物，并可作为镇痛疗效的预测因子。所有入选受试者的血浆IL-12、TNF-1、P物质（SP）、热休克蛋白70 （HSP70）、亚硝酸盐水平（测量一氧化氮合酶活性）和胍丁氨酸的基线水平将在定期医院就诊期间测定。这些血浆标志物的水平将在急性疼痛危重症急诊期间和出院前测量。生物标志物的最终分析将在急性疼痛危机后2至4周的预定访问期间进行。总之，这项研究将产生两组基本的初步数据，这两组数据都将允许更深入地评估SCD疼痛综合征的机制和其他治疗方案。

DESCRIPTION (provided by applicant): Although extensive research has been conducted with children who have sickle cell disease, there is a paucity of studies on adults with the disease. Many adult patients with sickle cell disease (SCD) experience daily pain. Although the pathophysiology of sickle cell related pain is complex, microcirculatory occlusion with tissue ischemia and activation of inflammatory cascades are believed to be involved. Acute vasoocclusive crises are responsible for most sickle cell related medical visits. Despite strong evidence for a role of tissue and vascular inflammation in the initiation and maintenance of acute vasoocclusive crises, no specific serum biomarkers have been identified which correlate with the intensity or duration of the acute crisis. An effective mode of analgesic treatment that can be assessed by serum biomarker and improved has not been methodically investigated in SCD pain crisis. Therefore, the objective of this R21 proposal is to test the hypothesis that quality and method of analgesia affect the level of specific blood biomarkers and can be correlated with pain levels. Thus, this study would provide a unique opportunity to understand the treatment effects of sickle cell crisis on pain and provide a basis for future interventions and clinical use of specific serum biomarkers. The first aim is to test the hypothesis that the mode of analgesia technique affects the outcome of pain crisis as determined by pain scores, analgesic consumption and hospital admission rates in SCD pain crisis. The SCD subjects will be enrolled during a regular hospital visit (total target of 75 subjects) and followed up during the emergency visit for the acute pain crisis. The standard analgesic technique of parenteral and oral opiate treatment will used. The aim is to assess the effect of analgesic treatment on acute and subacute pain levels during and after an acute sickle pain crisis and to identify serum inflammatory/pain molecules as biomarkers for pain severity in SCD pain crisis and to test the hypothesis that serum biomarkers can be used to predict need for admission, increased need for analgesics, and possibly disease complication rates in SCD. Furthermore, to determine if the analgesic treatment influence serum biomarkers and can be used as a predictor of analgesic efficacy. The baseline levels of plasma IL-12, TNF-1, Substance P (SP), heat shock protein 70 (HSP70), nitrite levels (measure of nitric oxide synthase activity) and agmatine will be determined in all enrolled subjects during the regular hospital visit. The levels of these plasma markers will be measured during the emergency visit for acute pain crisis and before discharge. The final analysis of the biomarkers will be made during the scheduled visit at 2 to 4 weeks after the acute pain crisis. At the conclusion, this study will produce two basic sets of preliminary data both of which will allow a more in-depth evaluation of the mechanisms of SCD pain syndrome and other treatment options. PUBLIC HEALTH RELEVANCE: One of the objectives of this R21 program announcement is to develop translational research program where laboratory-based scientific discoveries are applied into practical/clinical settings in pain conditions. Accordingly, the objective of this Proposal is to evaluate the standard analgesic treatment option during sickle cell disease (SCD) pain crisis and to identify serum biomarkers that will predict the occurrences and for treatment outcome during pain crisis. Thus, this Proposal is well under the scope of the PA-06-542 as an exploratory proposal in attempting to understand the efficacy of analgesic treatment and whether novel serum biomarkers can be identified as useful tools for future studies in SCD pain crisis.