LONG ACTING OPIOIDS IN AMPUTATION PAIN MANAGEMENT

四肢截肢导致两种常见的疼痛类型，幻肢痛和 残肢痛。 幻痛是一种使人衰弱的神经性疼痛综合征 超过50%的截肢者都有这种情况 现有模式 对于这种顽固性的慢性疼痛状态的管理是不可靠的 更好的治疗是必要的 几种药理学和非药理学 已经提出了用于 治疗幻痛 然而，没有一种治疗方法 在对照研究中显示，在超过30%的 患者 这项建议的长远目标是发展得更好 用于缓解疼痛和相关的药物治疗 截肢后幻痛的功能限制。 我们特别 将评估慢性阿片类药物或美西律治疗是否会 显著改善疼痛和改善功能， 幻痛，仔细监测治疗并发症。 一 将对患者进行详细的精神评估，使用 在慢性疾病和疼痛中具有既定有效性的评估工具， 以确定是否存在终身和当前流行的共同- 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 注射利多卡因、吗啡和生理盐水（安慰剂）止痛， 在纳入研究前的不同日期以设盲方式测定 口服吗啡或美西律的治疗试验。 患者（N=108） 截肢后6个月持续性幻痛将入组 随机、双盲、安慰剂对照、交叉研究。 后 基线期，每例患者将接受3个治疗期： 安慰剂期和用美沙芬和吗啡的治疗期。 每个治疗期将包括药物减量、药物滴定（4 周）和维持治疗（2周）阶段。 在药物 逐渐减少阶段，任何先前的治疗将逐渐减少，而在 滴定阶段，研究药物将滴定至最大效应， 痛苦 患者将被随机分配至6个治疗组，以控制 治疗和顺序效应。 结果指标将评估损害 (pain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。 测量将在三次测量之前和结束时进行。 治疗周期。 任何合并症对治疗的影响， 安慰剂反应和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 静脉输液试验是否可以预测后续口服 用同样的药物治疗。 研究设计的优势包括：1） 允许受试者内比较的双盲交叉设计 与安慰剂相比，美西律和吗啡的疗效; 2） 治疗和顺序效果的控制。 拟定临床研究 可能会回答阿片类药物疗效的关键问题， 在体模和相关疾病的管理中使用美西律疗法 截肢者的神经性疼痛综合征。

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.