Analgesic technique on pain and biomarkers during sickle pain crisis

镰状痛危象期间疼痛和生物标志物的镇痛技术

基本信息

批准号：
7789477
负责人：
GAILEN D. MARSHALL
金额：
$ 22.35万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7789477
关键词：
Absence of pain sensation Accident and Emergency department Acute Acute Pain Address Admission activity Adult Affect Agmatine Ambulatory Care Facilities Analgesics Back Biological Markers Blood Child Child Care Clinic Clinic Visits Clinical Complex Complication Consumption Data Development Disease Emergency Situation Employment Enrollment Evaluation Exploratory/Developmental Grant Functional disorder Future Heat-Shock Proteins 70 Hematology Hospitals Inflammatory Interleukin-12 Intervention Ischemia Laboratories Link Maintenance Measures Medical Methods NIH Program Announcements Nitric Oxide Synthase Nitrites Opiates Oral Outcome Outpatients Pain Parents Patient Discharge Patients Plasma Process Refractory Regimen Research Role Schedule Serum Severities Sickle Cell Sickle Cell Anemia Substance P Syndrome Techniques Testing Time Tissues Translational Research Treatment outcome Visit base experience follow-up hospital admission rate improved inflammatory pain novel programs public health relevance sickle cell crisis sickling tool treatment effect vascular inflammation

项目摘要

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.

描述（由申请人提供）：尽管已经对患有镰状细胞病的儿童进行了广泛的研究，但对这种疾病的成年人的研究很少。许多成年患者患有镰状细胞病（SCD）每天疼痛。尽管镰状细胞相关疼痛的病理生理学是复杂的，但据信与组织缺血的微循环闭塞和炎症级联反应的激活被认为涉及。急性血管造成的危机导致大多数与镰状细胞有关的医疗就诊。尽管有充分的证据表明组织和血管炎症在急性血管造成的危机的启动和维持中的作用，但尚未确定与急性危机的强度或持续时间相关的特定血清生物标志物。在SCD疼痛危机中尚未有条不紊地研究一种可以通过血清生物标志物评估并改善的止痛治疗的有效模式。因此，该R21提案的目的是检验以下假设：镇痛的质量和方法会影响特定的血液生物标志物水平，并且可以与疼痛水平相关。因此，这项研究将提供一个独特的机会，以了解镰状细胞危机对疼痛的治疗效果，并为未来的干预措施和特定血清生物标志物的临床使用提供基础。第一个目的是检验以下假设：镇痛技术的模式会影响疼痛评分，SCD疼痛危机中疼痛评分，镇痛消费和住院率所确定的疼痛危机的结果。 SCD受试者将在常规医院访问期间（总数为75名受试者）参加，并在紧急访问中进行急性疼痛危机。肠胃外和口服阿片类药物的标准镇痛技术将使用。目的是评估止痛药治疗对急性镰状疼痛危机期间和之后的急性和亚急性疼痛水平的影响，并确定血清炎症/疼痛分子是SCD疼痛危机中疼痛严重程度的生物标志物，并测试可以使用血清生物标记物来预测录取需要的血清生物标志物，以预测需要增加Analge Analgeissickiss和可能的疾病差异。此外，为了确定镇痛治疗是否影响血清生物标志物，可以用作镇痛功效的预测指标。血浆IL-12，TNF-1，物质P（SP），热休克蛋白70（HSP70），亚硝酸盐水平（一氧化氮合酶活性的量度）和agmatine的基线水平均在常规医院期间的所有招聘受试者中确定。这些等离子体标记的水平将在紧急访问中以急性疼痛危机和出院前进行测量。急性疼痛危机后2至4周，将在预定的访问期间对生物标志物进行最终分析。最后，这项研究将产生两组基本的初步数据，这两个数据将允许对SCD疼痛综合征和其他治疗方案的机制进行更深入的评估。公共卫生相关性：该R21计划公告的目标之一是制定转化研究计划，以实验室的科学发现应用于疼痛条件下的实用/临床环境。因此，该提案的目的是评估镰状细胞疾病（SCD）疼痛危机期间的标准镇痛治疗选择，并确定将预测疼痛危机期间发生的事件和治疗结果的血清生物标志物。因此，该提案在PA-06-542的范围下很好地作为探索性建议，试图了解止痛治疗的功效，以及是否可以将新型血清生物标志物确定为SCD疼痛危机中未来研究的有用工具。