Opioid Self-Administration in Chronic Pain

阿片类药物自我给药治疗慢性疼痛

• 批准号: 7471173
• 负责人: Carolyn A Fairbanks
• 金额: $ 21.12万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471173
• 关键词: Absence of pain sensation; Adjuvant Therapy; Agmatine; Analgesics; Animals; Anticonvulsants; Antidepressive Agents; Anxiety; Automobile Driving; Chlordiazepoxide; Chronic; Clonidine; Condition; Daily; Dependence; Dose; Drug Delivery Systems; Fentanyl; Fright; Future; Hyperalgesia; Hypersensitivity; Inbred Strain; Individual; Malignant Neoplasms; Mechanics; Mediating; Methods; Modeling; Motivation; Mus; Nerve; Neurons; Neuropathy; Opiates; Opioid; Opioid Analgesics; Pain; Pain management; Patients; Persistent pain; Predisposing Factor; Process; Public Health; Reaction; Reaction Time; Reducing Agents; Research; Rewards; Self Administration; Self-Administered; Spinal; Tactile; Taxonomy; Techniques; Therapeutic; Therapeutic Agents; Thinking; Week; addiction; cancer pain; chronic pain; concept; day; experience; improved; indexing; injured; insight; motivated behavior; mouse model; programs; response; tumor

DESCRIPTION (provided by applicant): Opioids remain the most effective pharmacotherapeutics for the treatment of many chronic pain conditions. However, the potential for misuse of opioids can impact the decision to use them, particularly in the treatment of non-cancer pain. Opioid tolerance, dependence, addiction and some chronic pain conditions all share common mechanisms of neuronal adaptation. Consequently, distinguishing between these responses in an individual is challenging. Central drug delivery methods (e.g. intrathecal) enable some separation of chronic pain mechanisms (in large part spinally mediated) from those driving motivated behavior (supraspinally mediated). The proposed research program will use these techniques in experimental murine models of chronic pain to separate fentanyl self-administered (orally) for relief of chronic hyperalgesia from opioid self- administered in excess of that required for relief of hyperalgesia (anti-hyperalgesia). Experimental subjects with induced chronic neuropathic or cancer-evoked hyperalgesia of the hindpaw will be allowed to self-administer opioid orally under operant control daily for four weeks; the resulting anti-hyperalgesia will be determined after each operant session. Rescue anti-hyperalgesic agents will be administered intrathecally on various days after induction of hyperalgesia to assess the impact of spinal anti-hyperalgesia on opioid self-administration. Determining the effect of spinally administered rescue analgesic on opioid self-administration will enable an assessment of the amount of opioid administered for anti-hyperalgesia independent of that self-administered for supraspinally mediated reward. Those subjects continuing to self-administer opioid in the presence of adequate spinal analgesic will be further evaluated to determine supraspinal mechanisms that pre-dispose them to opioid self-administration in excess of that required for anti-hyperalgesia. Conversely, experimental subjects that reduce opioid self-administration in response to spinal analgesic (for alleviation of mechanical hyperalgesia) will be evaluated for factors that protect them from excess opioid self-administration. Clarification of the conditions under which opioids are misused when given for treatment of chronic pain may better inform the decision-to-treat process. PUBLIC HEALTH RELEVANCE: Chronic pain sufferers are thought to take opiate analgesics more for pain relief than in search of reward; however, fear of abuse liability often limits their use, resulting in undertreatment of chronic pain. The relationship between opiate self-administration and chronic pain intensity is rarely studied in experimental animals. Modeling opioid self- administration in mice experiencing chronic pain will provide insight into this concept and ultimately improve patient access to opioid therapy for their pain.

描述（由申请人提供）：阿片类药物仍然是治疗许多慢性疼痛病症的最有效的药物治疗剂。然而，滥用阿片类药物的可能性可能会影响使用它们的决定，特别是在治疗非癌症疼痛时。阿片类药物的耐受性、依赖、成瘾和一些慢性疼痛都有共同的神经元适应机制。因此，区分个体的这些反应是具有挑战性的。中枢给药方法（例如鞘内给药）可以将慢性疼痛机制（大部分是脊髓介导的）与驱动动机行为的机制（脊髓上介导的）分开。拟议的研究计划将在慢性疼痛的实验鼠模型中使用这些技术，将用于缓解慢性痛觉过敏的自我给药（口服）芬太尼与超过缓解痛觉过敏（抗痛觉过敏）所需的阿片类药物分开。患有慢性神经性或癌症诱发后爪痛觉过敏的实验对象将被允许每天在操作控制下自行口服阿片类药物，持续四个星期； the resulting anti-hyperalgesia will be determined after each operant session.将在诱导痛觉过敏后的不同天鞘内给予救援抗痛觉过敏剂，以评估脊髓抗痛觉过敏对阿片类药物自我给药的影响。确定脊髓给药的救援镇痛剂对阿片类药物自我给药的影响将能够评估用于抗痛觉过敏的阿片类药物的给药量，而与脊髓上介导的奖励的自我给药量无关。将进一步评估那些在足够的脊髓镇痛剂存在下继续自我施用阿片类药物的受试者，以确定使他们预先倾向于阿片类药物自我施用超过抗痛觉过敏所需的脊髓上机制。相反，将评估因脊髓镇痛而减少阿片类药物自我给药（以减轻机械性痛觉过敏）的实验受试者，以了解保护他们免受过量阿片类药物自我给药的因素。澄清阿片类药物在治疗慢性疼痛时被滥用的情况可能会更好地为治疗决策过程提供信息。 公众健康相关性：慢性疼痛患者服用阿片类镇痛药更多的是为了缓解疼痛，而不是为了寻求回报；然而，对滥用责任的恐惧往往限制了它们的使用，导致慢性疼痛治疗不足。很少在实验动物中研究阿片类药物自我给药与慢性疼痛强度之间的关系。对经历慢性疼痛的小鼠进行阿片类药物自我给药建模将深入了解这一概念，并最终改善患者接受阿片类药物治疗的机会。