Clinical and Genetic Characteristics of Opioid Addiction in Chronic Pain

慢性疼痛阿片类药物成瘾的临床和遗传特征

• 批准号: 8221174
• 负责人: CHARLES P O'BRIEN
• 金额: $ 60.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8221174
• 关键词: Alcohol or Other Drugs use; Analgesics; Animals; Behavior; Behavioral; Behavioral Genetics; Blood specimen; Candidate Disease Gene; Characteristics; Chronic; Clinical; Comorbidity; Complex; Control Groups; Counseling; Country; Data; Dependence; Development; Diagnosis; Ensure; Exposure to; Genetic; Genetic Risk; Genotype; Goals; High Prevalence; Individual; Interview; Logistic Regressions; Measures; Monitor; Opiate Addiction; Opioid; Opioid Analgesics; Pain; Patients; Persistent pain; Pharmaceutical Preparations; Physicians; Policies; Prevalence; Property; Protocols documentation; Psychometrics; Psychosocial Factor; Questionnaires; Receptor Gene; Recording of previous events; Recovery; Reporting; Rewards; Risk; Risk Factors; Sample Size; Self-Injurious Behavior; Series; Socioeconomic Factors; Substance Use Disorder; Symptoms; Testing; Visit; Withdrawal; addiction; base; chronic pain; craving; genome wide association study; genome-wide analysis; instrument; non-cancer pain; opioid abuse; prescription opioid; prescription opioid abuse; prospective; standard of care; tool

DESCRIPTION (provided by applicant): Clinicians managing patients with chronic non-cancer pain (CNCP) are typically faced with the dilemma of providing the appropriate standard of care to alleviate suffering including the use of opioids, while not complicating recovery by exposing the vulnerable patient to the potential of opioid abuse and addiction. It has been considered the standard of care to provide patients suffering from CNCP with opioids, even on a long- term basis. However, there is ongoing debate regarding this policy of responsible opioid prescribing in chronic pain patients given the rising prevalence of prescription opioid abuse and addiction in the country (Johnston, 2008). Numerous studies have identified high prevalence rates of substance use disorder in chronic pain patients (Polantin, Kinney et al, 1993~ Compton et al, 1998~ Martell et all, 2006). Reported prevalence of opioid abuse in chronic pain patients ranges from 3-40% (Fishbain et al, 1992, 2008~ Martell et al, 2007~ Ives et al, 2006). Diagnosing abuse and addiction in patients with chronic pain on opioids is very complex. It is difficult to ascertain who will become problematic users of prescription opioids when initiating therapy. There have been attempts at mitigating this problem of predicting which patients are at risk for opioid addiction (OA), with the utilization of questionnaires and interview protocols which have been promising, but not well validated (Turk et al, 2008). This project is the first in a series of studies to assess the behavioral and genotypic characteristics of patients who develop OA. There is a growing body of evidence indicating that risk for OA has substantial genetic origins (Kreek et al, 2005). There has been considerable evidence from clinical and animal studies regarding the mu opioid receptor (MOR) gene (OPRM1) as critical to the rewarding and analgesic properties of opioid analgesics. It is the specific aim of this project to perform genome-wide analysis in approximately 2,000 patients with CNCP having been treated for OA. To date it has been difficult to identify a control group of patients who are chronically exposed to opioids but do not develop addiction. In our study, 2000 patients with chronic pain who are receiving long-term opioid therapy and who have not displayed evidence of addiction will serve as our controls. In addition, we will assess psychiatric co-morbidities, aberrant behaviors, substance use, addiction and socioeconomic factors in both groups. This will allow us to substantiate in the control group the absence of addiction and also to elucidate specific psychosocial factors and specific behaviors in the experimental group suggestive of addiction. This data will form the basis of subsequent studies in developing behavioral and genetic risk profiling for prospective testing in patients with chronic pain initiating opioid therapy. PUBLIC HEALTH RELEVANCE: This project is the first in a series of studies to assess the behavioral and genotypic characteristics of patients who develop opioid addiction. It is the specific aim of this project to perform genome-wide analysis in approximately 2000 patients with chronic non cancer pain having been treated for opioid addiction and a control group of 2000 pain patients maintained on chronic opioid therapy not displaying signs of addiction. This data will form the basis of subsequent studies in developing behavioral and genetic risk profiling for prospective testing in patients with chronic pain initiating opioid therapy.

描述(由申请人提供)：管理慢性非癌症疼痛(CNCP)患者的临床医生通常面临两难境地：既要提供适当的护理标准来减轻痛苦，包括使用阿片类药物，又不能使脆弱的患者暴露于阿片类药物滥用和成瘾的可能性，从而使康复复杂化。向CNCP患者提供阿片类药物，即使是长期的，也被认为是护理的标准。然而，鉴于处方阿片类药物滥用和成瘾在该国日益普遍，关于在慢性疼痛患者中负责任地开出阿片类药物这一政策的争论仍在继续(Johnston，2008年)。许多研究已经证实了慢性疼痛患者中物质使用障碍的高患病率(Polantin，Kinney等人，1993~Compton等人，1998~Martell et all，2006)。报告的阿片类药物滥用在慢性疼痛患者中的流行率从3%到40%不等(Fishbain等人，1992,2008~Martell等人，2007~Ives等人，2006)。诊断阿片类药物慢性疼痛患者的滥用和成瘾非常复杂。很难确定在开始治疗时，谁会成为处方阿片类药物的问题使用者。有人试图通过利用问卷和访谈协议来缓解这一预测哪些患者有阿片成瘾(OA)风险的问题，这些方法很有希望，但没有得到很好的验证(Turk等人，2008年)。该项目是一系列研究中的第一个，该研究评估了患有骨性关节炎患者的行为和基因特征。越来越多的证据表明，骨性关节炎的风险有实质性的遗传根源(Kreek等人，2005年)。临床和动物研究已有相当多的证据表明，Mu阿片受体基因(OPRM1)对阿片类镇痛剂的奖赏和止痛特性至关重要。该项目的具体目标是对大约2,000名接受过骨性关节炎治疗的CNCP患者进行全基因组分析。到目前为止，很难确定长期接触阿片类药物但没有成瘾的对照组患者。在我们的研究中，2000名正在接受长期阿片类药物治疗的慢性疼痛患者将作为我们的对照组，他们没有表现出成瘾的证据。此外，我们还将评估两组患者的精神共病、异常行为、药物使用、成瘾和社会经济因素。这将使我们能够证实控制组中没有上瘾，也可以阐明试验组中特定的心理社会因素和暗示成瘾的特定行为。这些数据将成为后续研究的基础，开发行为和遗传风险简档，用于对启动阿片类药物治疗的慢性疼痛患者进行前瞻性测试。 公共卫生相关性：该项目是评估阿片成瘾患者的行为和基因特征的一系列研究中的第一个。该项目的具体目标是对大约2000名接受阿片成瘾治疗的慢性非癌症疼痛患者和2000名接受长期阿片类药物治疗但没有表现出成瘾迹象的疼痛患者进行全基因组分析。这些数据将成为后续研究的基础，开发行为和遗传风险简档，用于对启动阿片类药物治疗的慢性疼痛患者进行前瞻性测试。