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.

四肢截肢会导致两种常见类型的疼痛：幻痛和幻痛。 残肢疼痛。 幻痛是一种使人衰弱的神经性疼痛综合征 超过 50% 的截肢者都会出现这种情况。 目前可用的方式 对于这种顽固的慢性疼痛状态的治疗是不可靠的 并且需要更好的治疗方法。 一些药理和非 已提出药物治疗方案 治疗幻痛。 然而，所有的治疗方法均未见效 对照研究表明，对超过 30% 的患者有效 患者。 该提案的长期目标是更好地发展 减轻疼痛和相关疾病的药物疗法 截肢后幻痛的功能限制。 具体来说，我们 将评估慢性阿片类药物或美西律治疗是否会 显着减轻患者的疼痛并改善功能 幻痛，仔细监测治疗并发症。 一个 将对患者进行详细的精神评估，使用 在慢性疾病和疼痛方面具有明确有效性的评估工具， 以确定是否存在终生和当前的共同患病率 病态精神疾病影响治疗结果 吗啡、美西律或安慰剂。 静脉推注的影响 输注利多卡因、吗啡和生理盐水（安慰剂）可缓解疼痛 在纳入之前的不同日子以隐蔽方式确定 口服吗啡或美西律的治疗试验。 患者 (N=108) 截肢后 6 个月出现持续性幻痛将被纳入 随机、双盲、安慰剂对照、交叉研究。 经过一个 无药基线期，每位患者将经历3个治疗期： 安慰剂期和美西律和吗啡治疗期。 每个治疗周期将包括药物逐渐减量、药物滴定（4 周）和维持治疗（2 周）阶段。 服药期间 逐渐减少阶段，之前的任何治疗都将逐渐减少，而在逐渐减少阶段 滴定阶段 研究药物将滴定至最大效果 疼痛。 患者将被随机分为 6 个治疗组以进行对照 处理和订单效果。 结果措施将评估减值 （疼痛强度、疼痛缓解、定量感觉测试）、物理 功能障碍和心理社会功能或障碍。 测量将在三个阶段中的每个阶段之前和结束时进行 治疗期。 任何合并症对治疗和治疗的影响 安慰剂反应以及阿片类药物的认知和/或情感并发症 和美西律治疗，将进行评估。 该研究还将评估 是否静脉注射输注测试可以预测后续口服治疗的成功 使用相同的药物进行治疗。 研究设计的优点包括：1) 双盲交叉设计，允许受试者内比较 美西律和吗啡与安慰剂相比的疗效以及 2) 控制治疗和订单效果。 拟议的临床研究 可能会回答阿片类药物功效的关键问题 美西律疗法在幻象和相关疾病管理中的应用 截肢者的神经性疼痛综合征。