Chronic pain and alcohol dependence

慢性疼痛和酒精依赖

• 批准号: 8569864
• 负责人: IGOR SPIGELMAN
• 金额: $ 22.14万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8569864
• 关键词: Abstinence; Acute; Adult; Adverse effects; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Intoxication; Alcoholism; Alcohols; Analgesics; Animal Model; Animals; Chronic; Clinical; Clinical Research; Clinical Treatment; Complex; Consumption; Data; Dependence; Development; Disease; Disulfiram; Effectiveness; Emotional; Entrapment Neuropathies; Ethanol; Future; Human; Hyperalgesia; Intake; Maintenance; Modeling; Naltrexone; Nerve Entrapment; Neuraxis; Neuropathy; Pain; Pattern; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Pilot Projects; Play; Population; Property; Rattus; Regimen; Relapse; Role; Source; Symptoms; Testing; United States National Institutes of Health; Withdrawal; acamprosate; addiction; alcohol use disorder; chronic neuropathic pain; chronic pain; craving; design; drinking; novel; public health relevance; relating to nervous system; research study; sciatic nerve; sham surgery; socioeconomics; transmission process

DESCRIPTION (provided by applicant): Chronic pain affects >50 million adults in the U.S. and represents a major socioeconomic and clinical challenge, in part because even the most efficacious of the current medications are limited by their side-effects profile. Similarly, alcoholism is a major problem with clinical treatments showing limited efficacy in reducing craving, relapse and abstinence rates. Clinical studies revealed a complicated association between chronic pain and alcohol dependence. Thus, chronic pain states significantly affect alcohol use patterns and promote the development of alcoholism, while long-term alcohol dependence induces symptoms of hyperalgesia and may exacerbate chronic pain arising from other sources. Alcohol's acute analgesic effects and chronic alcohol's hyperalgesic effects have been studied in animal models. However, the precise relationship between chronic pain and development of alcohol dependence has yet to be examined in animals, in part due to the lack of robust models that reflect the complex relationship between chronic pain and alcohol dependence in humans. In this exploratory project we propose 2 related specific aims designed to develop a robust animal model which reflects findings in humans and test specific hypotheses regarding the precise relationship between chronic pain and alcohol dependence. SA1 examines the dual consequences of alcohol dependence and chronic (neuropathic) pain development on voluntary alcohol drinking. This aim will be achieved through the combined use of three well-characterized rat models of: a) alcohol dependence induced by forced chronic intermittent ethanol (CIE) administration, b) peripheral neuropathy induced by sciatic nerve entrapment (SNE) and c) voluntary (2-bottle choice, 2BC) regimen of ethanol (EtOH) consumption. SA2 examines if chronic pain- induced increases in voluntary EtOH intake is due to the analgesic effects of EtOH. This aim will be achieved by first exposing rats to voluntary (2BC) regimen of EtOH consumption followed by EtOH withdrawal, SNE neuropathy induction and subsequent re-introduction of 2BC EtOH consumption. Upon 2BC EtOH re- introduction rats are provided with relief of neuropathy symptoms using unique novel analgesics without central nervous system side effects and their EtOH intake compared to that of vehicle-injected rats. In total, the experiments outlined in SA1 and SA2 will provide the much needed data on the role that chronic pain may play in the development and maintenance of alcohol dependence in robust, validated animal models. Future studies could make use of these models to further unravel the complex interactions between chronic pain and alcohol dependence, as well as test novel targeted treatments for these disorders.

描述（由申请人提供）：慢性疼痛影响美国超过 5000 万成年人，是一项重大的社会经济和临床挑战，部分原因是即使是当前最有效的药物也受到其副作用的限制。同样，酗酒是一个主要问题，临床治疗在降低烟瘾、复发和戒酒率方面效果有限。临床研究揭示了慢性疼痛与酒精依赖之间存在复杂的关联。因此，慢性疼痛状态显着影响酒精使用模式并促进酒精中毒的发展，而长期酒精依赖会诱发痛觉过敏症状，并可能加剧其他来源引起的慢性疼痛。酒精的急性镇痛作用和慢性酒精的痛觉过敏作用已在动物模型中进行了研究。然而，慢性疼痛与酒精依赖发展之间的确切关系尚未在动物身上得到检验，部分原因是缺乏反映人类慢性疼痛与酒精依赖之间复杂关系的稳健模型。在这个探索性项目中，我们提出了两个相关的具体目标，旨在开发一个稳健的动物模型，该模型反映了人类的发现，并测试了有关慢性疼痛和酒精依赖之间精确关系的具体假设。 SA1 检查酒精依赖和慢性（神经性）疼痛发展对自愿饮酒的双重后果。这一目标将通过联合使用三种特征良好的大鼠模型来实现：a）强制慢性间歇性乙醇（CIE）给药诱导的酒精依赖，b）坐骨神经卡压（SNE）诱导的周围神经病变和c）自愿（2瓶选择，2BC）乙醇（EtOH）消耗方案。 SA2 检查慢性疼痛引起的自愿乙醇摄入量增加是否是由于乙醇的镇痛作用。该目标将通过首先让大鼠接受自愿（2BC）EtOH 消耗方案，然后撤除 EtOH，诱导 SNE 神经病变并随后重新引入 2BC EtOH 消耗来实现。 2BC后，重新注射EtOH后，使用独特的新型镇痛药缓解了大鼠的神经病变症状，且没有中枢神经系统副作用，并且与注射媒介物的大鼠相比，它们的EtOH摄入量也得到了缓解。总的来说，SA1 和 SA2 中概述的实验将提供急需的数据，说明慢性疼痛在稳健、经过验证的动物模型中在酒精依赖的发展和维持中可能发挥的作用。未来的研究可以利用这些模型进一步揭示慢性疼痛和酒精依赖之间复杂的相互作用，并测试针对这些疾病的新颖的靶向治疗方法。