A staged, comprehensive investigation for developing insular deep brain stimulation to treat refractory chronic pain

项目摘要 难治性慢性疼痛患者通常对传统镇痛药或弱阿片类药物无反应 因为这些药物不能直接解决他们疼痛的原因。许多慢性疼痛患者没有 即使使用循证治疗也能达到令人满意的疼痛缓解，或者他们不能耐受有效的 剂量，因为不良副作用。脑深部电刺激（DBS）已经是一种公认的 难治性运动障碍和癫痫的治疗，以及 疼痛神经生理学和生物技术可能有助于DBS作为一种非药物治疗 治疗顽固性慢性疼痛。 在计划的第一阶段，我们将招募12名患有难治性神经性疼痛的受试者， 采用急性刺激和神经生理学大脑进行岛叶脑映射的住院临床试验 监测.用于刺激和记录的电极将被沿着 岛叶皮质的前后轴。在急性岛叶性疼痛期间具有阳性镇痛作用的受试者 第一阶段的刺激措施将继续到第二阶段， 一项随机、假刺激对照、双盲、交叉临床试验， DBS，目的是获得该手术的安全性和有效性数据。此外，我们的目标是 通过研究神经活动的变化来开发疼痛的神经生理学生物标志物。 从本研究中获得的安全性数据、效应量和岛叶刺激参数将用于 后续临床试验的设计。本项目中确定的神经生理学疼痛生物标志物 还将有助于开发一种新型的闭环岛屿DBS系统，以及新的 用于管理慢性疼痛的诊断/预后措施。如果被证明是安全有效的， DBS将为患有以下疾病的患者提供急需的非药物治疗选择： 顽固性慢性疼痛

PROJECT SUMMARY Patients with refractory chronic pain typically do not respond to traditional analgesics or weak opioids as these agents do not directly address the cause for their pain. Many chronic pain patients do not achieve satisfactory pain relief even with evidence-based treatment, or they do not tolerate effective doses because of adverse side effects. Deep brain stimulation (DBS) is already an established treatment for intractable movement disorders and epilepsy, and recent advancements in the fields of pain neurophysiology and biotechnology may facilitate the use of DBS as a nonpharmacological therapy for refractory chronic pain. In the first stage of the proposed project, we will enroll 12 subjects with refractory neuropathic pain to an inpatient clinical trial for insular brain mapping with acute stimulation and neurophysiological brain monitoring. Electrodes for stimulating and recording will be implanted stereotactically along the anterior-posterior axis of the insular cortex. Subjects with positive analgesic effects during acute insular stimulation in the first stage of the proposed project will continue to the second stage, which will consist of a randomized, sham-stimulation-controlled, double-blinded, cross-over clinical trial of chronic insular DBS with the purpose of obtaining safety and efficacy data for this procedure. Furthermore, we aim to develop neurophysiological biomarkers of pain by studying changes in neural activity. Safety data, effect size, and insular stimulation parameters obtained from this research will be used in the design of subsequent clinical trials. The neurophysiological pain biomarkers identified in this project will also aid the development of a novel, closed-loop insular DBS system, as well as new diagnostic/prognostic measures for managing chronic pain. If proven to be safe and effective, insular DBS will offer a much needed non-pharmacological treatment option for patients suffering from refractory chronic pain.