LONG ACTING OPIOIDS IN AMPUTATION PAIN MANAGEMENT

截肢会导致两种常见的疼痛类型，幻影和 残肢疼痛。幻觉疼痛是一种衰弱的神经病理性疼痛综合征 超过50%的截肢者会发生这种情况。目前可用的医疗模式 对于这种顽固的慢性疼痛状态的管理是不可靠的 更好的治疗方法是必要的。几种药理和非药理作用 药物治疗方案已被建议用于治疗 幻觉疼痛的治疗。然而，没有一种治疗方法是 在对照研究中显示，在超过30%的 病人。这项建议的长期目标是更好地发展 缓解疼痛的药物治疗及其相关 截肢后幻觉疼痛的功能局限性。具体来说，我们 将评估慢性阿片类药物或美西律治疗是否会 显著改善患者的疼痛和改善功能 幻觉疼痛，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 评估工具在慢性病和疼痛方面具有既定的有效性， 以确定有生之年和当前患病率是否为 病态精神疾病影响治疗结果 吗啡、美西律或安慰剂。静脉推注的效果 注入利多卡因、吗啡和生理盐水(安慰剂)治疗疼痛 在包含在 口服吗啡或美西律的治疗试验。患者(N=108) 截肢后6个月持续幻觉疼痛将参加 随机、双盲、安慰剂对照、交叉研究。在.之后 无药物基线期间，每个患者将经历3个疗程： 安慰剂期和美西律和吗啡的治疗期。 每个疗程将包括药物缩减、药物滴定(4 周)和维持治疗(2周)阶段。在服药期间 在缩减阶段，以前的任何治疗都将逐渐减少，而在 滴定阶段研究药物将被滴定到最大效果 疼痛。患者将被随机分成6个治疗组进行对照 治疗和秩序效应。结果衡量标准将评估损害 (疼痛强度、疼痛缓解、定量感觉测试)、身体 工作人员残疾，以及心理社会功能或残疾。 测量将在每一次测量之前和结束时进行 治疗周期。任何共病对治疗和治疗的影响 安慰剂反应与阿片类药物的认知和/或情感并发症 以及美西律治疗，将进行评估。这项研究还将评估 无论是静脉注射。输液测试可以预测后续口腔治疗的成功 用同样的药物进行治疗。研究设计的优点包括：1) 双盲交叉设计，允许进行受试者内比较 美西律和吗啡与安慰剂的疗效对比和2) 治疗和秩序影响的控制。建议的临床研究 可能会回答阿片类药物疗效的关键问题 美西律治疗幻觉及相关疾病 截肢者的神经病理性疼痛综合征。

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.