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

Mu 阿片类药物多态性作为疼痛的基因修饰剂和阿片类药物的使用

• 批准号: 8410044
• 负责人: Robert William Gibson
• 金额: $ 7.01万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-16 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8410044
• 关键词: Acute Pain; Address; COMT gene; Candidate Disease Gene; Caring; Chronic; Coupled; Data; Data Collection; Data Correlations; Dependence; Dependency; Dose; Enrollment; Evolution; Fetal Hemoglobin; Frequencies; Fright; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Haplotypes; Healthcare; Heterogeneity; Hospitalization; Individual; Information Resources Management; Lead; Leg Ulcer; Length of Stay; Morphine; Narcotics; National Center on Minority Health and Health Disparities; Necrosis; Opioid; Opioid Analgesics; Opioid Peptide; PTGS1 gene; PTGS2 gene; Pain; Pain Threshold; Pain intensity; Pain management; Pain-Free; Patients; Perception; Pharmaceutical Preparations; Provider; Sickle Cell; Sickle Cell Anemia; Site; Testing; Variant; addiction; base; chronic pain; diaries; digital; endogenous opioids; experience; improved; mu opioid receptors; pressure; prospective; response

Vasoocclusive episodes (VOE; painful crises) are a well-known hallmark of sickle cell disease (SCD) 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. SCD 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 SCD. 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 SCD.

血管闭塞性发作（VOE;痛苦的危机）是镰状细胞病（SCD）的一个众所周知的标志，并且是绝大多数医疗保健遭遇的原因。这些患者中VOE（急性疼痛）的频率存在显著异质性。SCD患者还经历由于诸如缺血性坏死和腿部溃疡的并发症引起的慢性疼痛。虽然这种异质性中的一些可以通过众所周知的遗传修饰剂（例如血红蛋白F）来解释，但是存在大量患者，其中对于这种变异缺乏明确的解释。阿片类药物是SCD患者急性和慢性疼痛管理的重要组成部分。长期使用阿片类药物，有时与一部分患者的依赖和成瘾有关，可能会造成难以管理的问题。再加上对疼痛管理普遍缺乏足够的知识和对成瘾的恐惧，往往导致对疼痛状况的治疗不足。Mu阿片受体（OPRM 1）是内源性阿片肽和阿片类镇痛药的主要作用部位。最近的数据表明，OPRM 1基因以及其他基因（COMT，PTGS 1，PTGS 2，SLC 6A 4，SCN 9A）的多态性与 疼痛阈值和麻醉剂需求的差异。这项研究将检验这一假设，即这些基因的变异作为影响疼痛频率、强度、阈值、阿片类药物使用和剂量要求以及阿片类药物依赖性的遗传修饰剂。这将通过以下方式实现：1）对VOE频率、疼痛日记和总阿片类药物使用进行前瞻性分析，2）前瞻性数据收集，包括VOE住院频率、住院VOE期间麻醉剂使用、疼痛评分的演变和住院时间以及这些数据与上述基因中遗传变异的相关性，3）用压力式疼痛计测试痛阈的实验部分。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SCD患者疼痛管理的个体化。