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

项目总结 顽固性慢性疼痛的患者通常对传统止痛药或弱阿片类药物没有反应 因为这些药物没有直接解决他们疼痛的原因。许多慢性疼痛患者并不这样做 即使通过循证治疗也能获得令人满意的疼痛缓解，或者他们不能耐受有效的疼痛 剂量，因为有不良副作用。脑深部刺激(DBS)已经是一种成熟的 顽固性运动障碍和癫痫的治疗，以及在以下领域的最新进展 疼痛神经生理学和生物技术可能促进DBS作为非药理学药物的使用 顽固性慢性疼痛的治疗。 在拟议项目的第一阶段，我们将招募12名患有顽固性神经病理性疼痛的受试者 急性刺激岛脑地形图与神经生理学脑电地形图的临床研究 监控。用于刺激和记录的电极将沿脑部立体植入 岛叶皮质的前后轴线。在急性岛叶期间有积极止痛作用的受试者 拟议项目第一阶段的刺激将继续到第二阶段，这将包括 一项随机、假刺激对照、双盲、交叉的慢性胰岛临床试验 DBS，目的是获得该程序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生物标记物。 从这项研究中获得的安全数据、效应大小和岛状刺激参数将用于 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记物 还将帮助开发一个新的、闭环系统的孤岛DBS系统，以及新的 治疗慢性疼痛的诊断/预后措施。如果被证明是安全有效的，与世隔绝 星展银行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.