An Animal Model of Therapeutic Self-Medication for Neuropathic Pain

描述(由申请人提供)：本申请“治疗神经病理性疼痛的动物模型”涉及广泛的挑战领域(15)翻译科学和具体挑战主题，15-DA-112：临床前慢性疼痛研究的新模型和措施。我们的长期目标是发现抑制人类缺乏药物滥用责任的病理性疼痛的机制。该应用程序的目的是验证用于评估非精神活性止痛药的治疗性自我用药的动物模型。我们的新方法结合了对止痛剂自我给药行为的评估与对抗伤害感觉和依赖的行为评估。我们的中心假设是，动物会自我用非精神活性大麻素止痛剂来减轻神经病理性疼痛状态。这些研究具有创新性，因为它们利用了通常用于研究滥用药物的积极强化效应的技术方法，并将这些方法应用于新的背景。在这里，药物自我给药被用来研究假定的镇痛剂的负面强化特性(即减轻神经病理性疼痛状态的能力)和在存在和不存在神经损伤的情况下的依赖倾向。研究人员能够很好地开展这项拟议的工作，因为我们开发了一种新的临床前模型，该模型表明动物将自我给予一种非精神活性大麻素止痛剂来减轻神经病理性疼痛状态。因此，我们相信我们的自我治疗模式具有广泛的翻译价值。我们将完成在两个特定目标下提出的实验：1)测试大鼠将自我给予非精神活性大麻类止痛剂以减轻神经病理性疼痛状态的假设，2)测试非精神活性大麻类止痛剂将产生相对于鸦片类止痛剂吗啡的最小依赖(拮抗剂催促的戒断和条件性位置厌恶)的假设。该项目的完成预计将验证一种新的临床前模型，用于评估止痛效果和药物滥用倾向。开发有效的疼痛药物疗法，将滥用的可能性降至最低，预计将降低医疗保健成本，减轻患者的痛苦。 与公共健康相关：疼痛是美国人获得医疗保健系统的头号原因。疼痛治疗不当造成的社会经济成本估计为每年1000亿美元。这项拟议的工作将开发和验证止痛药治疗性自我给药的大鼠模型。开发安全有效、没有滥用潜力的药物对于降低医疗保健成本和提高患者的生活质量是必要的。

DESCRIPTION (provided by applicant): The present application "An Animal Model of Therapeutic Self-Medication for Neuropathic Pain" addresses the broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DA-112: New Models and Measures in Preclinical Chronic Pain Research. Our long-term goal is to uncover mechanisms for suppressing pathological pain that lack drug abuse liability in humans. The objective of this application is to validate an animal model for assessing therapeutic self-medication of non-psychoactive analgesics. Our novel approach combines assessments of analgesic self-administration behavior with behavioral assessments of antinociception and dependence. Our central hypothesis is that animals will self-medicate with a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state. These studies are innovative because they exploit technological approaches commonly employed to study positive reinforcing effects of abused drugs and apply these methods to a novel context. Here, drug self-administration is used to study negative reinforcing properties of putative analgesics (i.e. ability to attenuate a neuropathic pain state) and dependence liability in the presence and absence of nerve injury. The investigators are well-positioned to conduct the proposed work because we have developed a new preclinical model which demonstrates that animals will self-administer a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state. We, consequently, believe that our self-medication model has broad translational value. We will complete experiments proposed under two Specific Aims: 1) To test the hypothesis that rats will self-administer a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state, 2) To test the hypothesis that a nonpsychoactive cannabinoid analgesic will produce minimal dependence (antagonist-precipitated withdrawal and conditioned place aversion), relative to the opiate analgesic morphine. Completion of this project is expected to validate a novel preclinical model for assessing both analgesic efficacy and drug abuse liability. The development of effective pharmacotherapies for pain with minimal abuse liability is expected to drive down health care costs and alleviate suffering in patients. PUBLIC HEALTH RELEVANCE: Pain is the number one reason Americans access the health care system. Socioeconomic costs of inadequate treatment for pain are estimated at $100 billion annually. The proposed work will develop and validate a rat model for therapeutic self-medication of analgesics. Development of safe and effective drugs that lack abuse potential is necessary to drive down health care costs and improve quality of life in patients.