Mu Opioid Polymorphisms as Genetic Modifiers of Pain and Opioid Use in

血管闭塞发作(VOE；痛苦的危象)是镰状细胞病(SCO)和 对绝大多数的医疗事故负有责任。有显著的异质性，在 这些患者中发生VOE(急性疼痛)的频率。SCO患者也会经历慢性疼痛，原因是 并发症，如缺血性坏死和腿部溃疡。虽然这种异质性中的一些可能是 由众所周知的遗传修饰物，如血红蛋白F解释，有大量的患者在 对于这种变化缺乏明确的解释。阿片类药物构成了 SCO患者急慢性疼痛的处理。慢性阿片类药物使用，有时与 在一部分患者中存在依赖和成瘾，可能会带来困难的管理问题。这 再加上普遍缺乏足够的疼痛管理知识和对上瘾的恐惧 往往会导致疼痛状况得不到足够的治疗。Mu阿片受体(OPRM1)是 内源性阿片肽和阿片类镇痛剂的作用。最近的数据表明，基因中的多态 OPRM1基因以及其他基因(COMT、PTGS1、Ptgs2、SLC6A4、SCN9A)与 痛阈值和麻醉剂需求量的差异。这项研究将检验这样一种假设，即 这些基因作为遗传修饰物影响疼痛的频率、强度、阈值、阿片类药物的使用和剂量 需求以及阿片类药物依赖。这将通过1)对频率进行前瞻性分析来实现 VOE、疼痛日记和阿片类药物总使用量，2)前瞻性数据收集，包括 VOE的住院情况、住院期间的麻醉药物使用、疼痛评分的演变以及VOE的持续时间 住院时间和这些数据与上述基因遗传变异的相关性，以及3)A 压力式痛觉计测痛阈值实验部分。预计 将确定疼痛频率和阿片类药物剂量需求的遗传相关性，并将导致 自发性硬化症患者疼痛管理的个体化。

Vasoocclusive episodes (VOE; painful crises) are a well-known hallmark of sickle cell disease (SCO) and are responsible for the vast majority of health care encounters. There is significant heterogeneity in the frequency of VOE (acute pain) among these patients. SCO patients also experience chronic pain due to complications such as avascular necrosis and leg ulcers. While some of this heterogeneity can be explained by well known genetic modifiers, such as the hemoglobin F, there is a large number of patients in whom there is a lack of a clear-cut explanation for this variation. Opioids form an important component of the management of acute and chronic pain in patients with SCO. Chronic opioid use, sometimes associated with dependence and addiction in a subset of patients, may pose difficult management problems. This coupled with a general lack of adequate knowledge of the management of pain and the fear of addiction often results in under-treatment of painful conditions. The Mu opioid receptor (OPRM1) is the primary site of action of endogenous opioid peptides and opioid analgesics. Recent data indicate that polymorphisms in the OPRM1 gene as well as other genes (COMT, PTGS1, PTGS2, SLC6A4, SCN9A) are associated with differences in pain threshold and narcotic requirements. This study will test the hypothesis that variations in these genes act as genetic modifiers influencing pain frequency, intensity, threshold, opioid usage and dose requirement, as well as opioid dependency. This will be achieved by 1) a prospective analysis of frequency of VOE, pain diaries, and total opioid usage, 2) a prospective data collection consisting of frequency of hospitalizations with VOE, narcotic usage during a hospitalized VOE, evolution of pain scores, and length of hospital stay and correlation of these data with genetic variation in the aforementioned genes, and 3) an experimental component of testing pain threshold with a pressure pain algometer. It is anticipated that genetic correlates of pain frequency and opioid dose requirements will be determined and will lead to individualization of the management of pain in patients with SCO.