LONG ACTING OPIOIDS IN AMPUTATION PAIN MANAGEMENT

长效阿片类药物治疗截肢疼痛

• 批准号: 6354092
• 负责人: SRINIVASA N. RAJA
• 金额: $ 26.21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6354092
• 关键词: amputation; analgesia; chronic disease /disorder; clinical research; drug screening /evaluation; human subject; human therapy evaluation; medical rehabilitation related tag; mexiletine; morphine; nervous system disorder chemotherapy; pain

Amputation of extremities leads to two common types of pain, phantom and stump pain. Phantom pain is a debilitating neuropathic pain syndrome that occurs in more than 50% of amputees. Presently available modalities for the management of this intractable, chronic pain state are unreliable and better therapies are necessary. Several pharmacological and non- pharmacological therapeutic regimens have been suggested for the treatment of phantom pain. However, none of the treatments have been shown, in controlled studies, to be effective in more than 30% of patients. The long-term objective of this proposal is to develop better pharmacological therapies for alleviating the pain and associated functional limitations of postamputation phantom pain. Specifically, we will assess whether chronic opioid or mexiletine therapy will significantly ameliorate pain and improve function in patients with phantom pain, monitoring carefully for treatment complications. A detailed psychiatric evaluation of patients will be conducted, using assessment tools with established validity in chronic illness and pain, to determine if the presence of lifetime and current prevalence of co- morbid psychiatric illness affects the outcome of treatment with morphine, mexiletine, or placebo. The effects of intravenous bolus infusions of lidocaine, morphine, and saline (placebo) on pain will be determined in a masked fashion on separate days prior to inclusion in the treatment trials with oral morphine or mexiletine. Patients (N=108) with persistent phantom pain 6 months after amputation will be enrolled in a randomized, double-blind, placebo-controlled, crossover study. After a drug-free baseline period, each patient will undergo 3 treatment periods: a placebo period and treatment periods with mexiletine and morphine. Each treatment period will consist of drug taper, drug titration (4 weeks), and maintenance treatment (2 weeks) phases. During the drug taper phase, any previous therapy will be tapered off, while during the titration phase the study drug will be titrated to maximal effect on pain. Patients will be randomized to 6 treatment groups to control for treatment and order effects. Outcome measures will assess impairment (pain intensity, pain relief, quantitative sensory tests), physical functioner disability, and psychosocial function or handicap. Measurements will be made before and at the end of each of the three treatment periods. The impact of any co-morbid illness on treatment and placebo response, and cognitive and/or affective complications of opioid and mexiletine therapy, will be evaluated. The study will also evaluate whether i.v. infusion tests can predict the success of subsequent oral therapy with the same drugs. Strengths of the study design include: 1) double-blind cross-over design that will allow within-subject comparisons of the efficacy of both mexiletine and morphine versus placebo and 2) controls for treatment and order effects. The proposed clinical studies are likely to answer the crucial question of the efficacy of opioid and mexiletine therapies in the management of phantom and associated neuropathic pain syndromes in amputees.

四肢的截肢导致两种常见类型的疼痛，幻影和 树桩疼痛。 幻影疼痛是一种令人衰弱的神经性疼痛综合征 这发生在超过50％的截肢者中。 目前可用的方式 为了管理这种棘手的慢性疼痛状态不可靠 并且需要更好的疗法。 几个药理和非 - 已经提出了药理学治疗方案 幻影疼痛的治疗。 但是，没有一种治疗方法 在对照研究中显示的是有效的30％以上 患者。 该建议的长期目标是更好地发展 减轻疼痛和相关的药理疗法 幻影后疼痛的功能局限性。 具体来说，我们 将评估慢性阿片类药物或墨西哥氨酸疗法是否会 明显缓解疼痛并改善患者的功能 幻影疼痛，仔细监测治疗并发症。 一个 将对患者进行详细的精神病评估 评估工具在慢性病和疼痛方面具有既定有效性， 确定寿命的存在和共同流行率是否存在 病态的精神病会影响治疗的结果 吗啡，墨西哥氨酸或安慰剂。 静脉注射的作用 利多卡因，吗啡和盐水（安慰剂）疼痛的输注将是 在包含在包含之前的几天之前以蒙面方式确定 口服吗啡或墨西哥氨酸的治疗试验。 患者（n = 108） 截肢后6个月持续的幻影疼痛将在A中注册 随机，双盲，安慰剂对照，跨界研究。 之后 无药物基线期，每个患者将接受3个治疗期： 墨西哥氨酸和吗啡的安慰剂期和治疗期。 每个治疗期将包括药物锥度，药物滴定（4个 周）和维护治疗（2周）阶段。 在药物期间 锥相，任何先前的疗法都会逐渐减小，而在 滴定阶段研究药物将被滴定以最大程度地对 疼痛。 患者将被随机分为6个治疗组，以控制 治疗和秩序效应。 结果指标将评估损害 （疼痛强度，缓解疼痛，定量感觉测试），物理 功能师残疾，社会心理功能或障碍。 测量将在三个之前和结尾处进行 治疗期。 任何联合疾病对治疗和 安慰剂反应以及阿片类药物的认知和/或情感并发症 将评估墨西哥氨酸疗法。 该研究还将评估 是否i.v.输注测试可以预测随后的口服的成功 用相同药物的治疗。 研究设计的优势包括：1） 双盲跨界设计将允许受试者内部比较 梅克西汀和吗啡与安慰剂的功效以及2） 控制治疗和秩序效应。 拟议的临床研究 很可能会回答阿片类药物疗效的关键问题 幻影管理和相关的梅克西汀疗法 截肢者中的神经性疼痛综合征。