Developing brain stimulation as a treatment for pain in opiate dependent individuals

摘要 有效控制慢性疼痛是美国的首要任务，因为大约10%的成年人 有严重的慢性疼痛-其中大部分是慢性下背痛（CLBP）。但尽管 尽管神经科学在过去20年里取得了很大的进步，但我们仍然主要用阿片类药物治疗慢性疼痛。 毒品，就像在内战中一样。除了他们的高滥用倾向和依赖性之外， 潜在的（1），只有30-40%的慢性疼痛患者声称他们获得了满意的（>50%）缓解， 通过药物治疗缓解疼痛。因此，迫切需要新的， 可以治疗疼痛并减少慢性疼痛患者对阿片类药物的依赖的治疗。 本R21提案的目标是评估2种新型无创脑刺激策略， 减轻疼痛和大脑对目前服用慢性阿片类药物的CLBP患者疼痛的反应。 经颅磁刺激（TMS）可以诱导长时程增强（LTP样）和长时程增强（LTP样）。 抑郁症（LTD样）以频率依赖的方式影响大脑活动。我们集团 先前的研究表明，LTP样TMS的背外侧前额叶皮层（DLPFC，一个节点， 执行控制网络（ECN））可以减少感知的疼痛和相应的BOLD信号 在“疼痛网络”中（策略1，目标1）。另一种策略是将类似LTD的刺激应用于 内侧前额叶皮层（MPFC，默认模式网络（DMN）中的一个节点;策略2，目标2）。 这项拟议的研究将首次采用随机、双盲、假对照设计， 参数评价10天rTMS对DLPFC（目标1）或 MPFC（目标2）对自我报告的疼痛和大脑对疼痛的反应。这将在一个队列中完成， 使用处方阿片类药物3个月或更长时间的慢性下背痛患者 没有足够的止痛效果患者将从综合疼痛管理中招募 MUSC诊所（由Borckardt博士，Co-I指导）和MUSC全科医学诊所。定量 疼痛测试和大脑对疼痛的反应性将在给药前和给药后10天立即测量。 TMS以及1个月和2个月随访（以评价耐久性）。

ABSTRACT Effective control of chronic pain is a top priority in the United States, as approximately 10% of adults have severe chronic pain – most of which is chronic lower back pain (CLBP). However, despite the advances in neuroscience over the past 20 years, we still largely treat chronic pain with opiate narcotics, much as was done in the Civil War. In addition to their high abuse liability and dependence potential (1), only 30–40% of chronic pain patients declare they receive satisfactory (>50%) relief from their pain through pharmacological treatment. Consequently there is a critical need for new, treatments that can treat pain and reduce reliance on opiates in individuals with chronic pain. The goal of this R21 proposal is to evaluate 2 novel non-invasive brain stimulation strategies to mitigate pain and the brain's response to pain in CLBP patients currently taking chronic opiates. Transcranial Magnetic Stimulation (TMS), can induce long term potentiation (LTP-like) and long term depression (LTD-like) effects on brain activity in a frequency dependent manner. Our group has previously demonstrated that LTP-like TMS to the dorsolateral prefrontal cortex (DLPFC, a node in the Executive Control Network (ECN)) can decrease perceived pain and corresponding BOLD signal in the “Pain Network” (Strategy 1, Aim 1). An alternative strategy is to apply LTD-like stimulation to the medial prefrontal cortex (MPFC, a node in the Default Mode Network (DMN); Strategy 2, Aim 2). The proposed study will be the first to employ a randomized, double-blind, sham-controlled design to parametrically evaluate the longitudinal effects of 10 days of rTMS to the DLPFC (Aim 1) or the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in a cohort of patients with chronic lower back pain that have been using prescription opiates for 3 or more months without adequate pain relief. Patients will be recruited from the comprehensive pain management clinic at MUSC (directed by Dr. Borckardt, Co-I) and MUSC General Medicine clinics. Quantitative Pain testing and Brain reactivity to pain will be measured immediately before and after 10 days of TMS as well as a 1 and 2 month follow-up (to evaluate durability).