Clinical and Genetic Characteristics of Opioid Addiction in Chronic Pain

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以下困境：提供适当的护理标准以减轻痛苦，包括使用阿片类药物，同时不使脆弱患者暴露于阿片类药物滥用和成瘾的可能性而使恢复复杂化。 向CNCP患者提供阿片类药物（即使是长期）已被视为标准治疗。 然而，鉴于该国处方阿片类药物滥用和成瘾的流行率不断上升，关于慢性疼痛患者中负责任的阿片类药物处方政策的辩论正在进行中（约翰斯顿，2008）。 许多研究已经确定慢性疼痛患者中物质使用障碍的高患病率（Polantin，Kinney et al，1993~ Compton et al，1998~ Martell et all，2006）。 据报告，慢性疼痛患者中阿片类药物滥用的患病率范围为3-40%（Fishbain et al，1992，2008~ Martell et al，2007~伊韦斯et al，2006）。 诊断阿片类药物慢性疼痛患者的滥用和成瘾非常复杂。 在开始治疗时，很难确定哪些人会成为处方类阿片的问题使用者。 已经尝试通过使用问卷调查和访谈方案来缓解预测哪些患者存在阿片类药物成瘾（OA）风险的问题，这些问卷调查和访谈方案很有希望，但尚未得到充分验证（Turk et al，2008）。 该项目是一系列评估OA患者行为和基因型特征的研究中的第一个。 越来越多的证据表明，OA风险具有显著的遗传来源（Kreek et al，2005）。 已有大量来自临床和动物研究的证据表明，μ阿片受体（莫尔）基因（OPRM 1）对阿片类镇痛药的奖赏和镇痛特性至关重要。 该项目的具体目标是对大约2,000名接受OA治疗的CNCP患者进行全基因组分析。 迄今为止，很难确定长期暴露于阿片类药物但不成瘾的对照组患者。 在我们的研究中，2000名接受长期阿片类药物治疗且未显示成瘾证据的慢性疼痛患者将作为我们的对照组。此外，我们将评估两组的精神共病、异常行为、物质使用、成瘾和社会经济因素。 这将使我们能够证实控制组中没有成瘾，并阐明实验组中暗示成瘾的特定心理社会因素和特定行为。 这些数据将成为后续研究的基础，为启动阿片类药物治疗的慢性疼痛患者的前瞻性测试开发行为和遗传风险分析。

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.