TMS in the Management of Postoperative Pain

描述（由申请人提供）：适当控制急性和慢性疼痛是医疗保健中最重要的领域之一。尽管神经科学取得了长足的进步，但术后疼痛控制仍严重依赖鸦片类麻醉品。这是一个问题，因为阿片类药物有时会导致成瘾，并伴有相当大的副作用，特别是在腹部手术后恢复的患者中，因为它们会直接阻碍肠道恢复，可能延长住院时间并延迟恢复。目前，似乎没有很好的替代候选药物用于术后疼痛控制。脑刺激控制疼痛是一个令人兴奋的新领域，它建立在关于疼痛功能神经解剖学的先进神经科学知识的基础上。皮质刺激现在可以通过经颅磁刺激（TMS）进行无创。几项研究表明，经颅磁刺激可以减轻健康成人和慢性疼痛患者的疼痛。最近，一项研究表明，在40例胃旁路手术后患者中，单次20分钟的经颅磁刺激（TMS）治疗左前额叶皮层（一个可能参与抑制疼痛情感层面的区域）可显著减少术后疼痛和患者自控镇痛（PCA）的使用，减少37%。然而，围绕这些初步发现的方法学问题限制了对经颅磁刺激控制术后疼痛有效性的明确结论。该R21提案将整合更严格的实验条件、真正的双掩模方法和更长期的后续评估。该R21的数据将为开展更大规模的明确研究TMS在控制术后疼痛方面的潜在临床应用和作用机制提供所需的信息。采用严格的双屏蔽方法，并在初步试点工作的基础上，我们提出（目的1）来测试左前额叶皮层重复经颅磁刺激是否能显著减少胃旁路手术后的术后疼痛和PCA的使用。我们还提出（目的2）确定经颅磁刺激的时间和剂量对术后疼痛和PCA使用的影响。最后，（目的3）我们建议在随访1个月、3个月和6个月时确定经颅磁刺激对术后恢复时间、临床结果和医疗费用的影响。132名参与者将被随机分配接受20分钟的活动前额叶经颅磁刺激或假前额叶经颅磁刺激，在胃旁路手术后45分钟。8小时后，参与者将被重新随机分配接受第二次治疗（真实或虚假）。参与者的PCA使用情况将与每天两次的术后疼痛和情绪视觉模拟量表评分一起被跟踪。该设计提供了4个条件，提供了与TMS时间和剂量对术后疼痛控制和长期临床结果的影响相关的信息。该试验的结果可能会提供大量关于皮质刺激对术后疼痛控制效用的信息。公共卫生相关性：适当控制急性和慢性疼痛是卫生保健最重要的领域之一，尽管神经科学取得了长足的进步，但术后疼痛控制严重依赖阿片类麻醉品。使用阿片类药物有许多风险，包括呼吸抑制、恶心和呕吐、咳嗽抑制、精神模糊、镇静和便秘，其中许多副作用对胃分流手术患者尤其严重，这些患者往往有呼吸问题（如阻塞性睡眠呼吸暂停）、右心室功能障碍、肺动脉高压，对他们来说，术后呕吐可能导致严重的并发症。因此，需要探索有可能减少这类患者术后对吗啡依赖的新干预措施，如经颅磁刺激。

DESCRIPTION (provided by applicant): The proper control of acute and chronic pain is one of the most important areas of health care. Despite profound advances in neuroscience, opiate narcotics are heavily relied upon for postoperative pain control. This is problematic as opiates can sometimes lead to addiction and are associated with considerable side effects that are especially problematic in patients recovering from abdominal surgery, as they can directly hinder gut recovery, likely prolong hospital stay and delay recovery. Presently, there do not appear to be good replacement pharmacological candidates for postoperative pain control. Brain stimulation for pain control is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neuroanatomy of pain. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). Several studies have shown that TMS can reduce pain in healthy adults and patients with chronic pain. Recently, it was shown that a single 20-minute treatment of TMS over the left-prefrontal cortex (an area that is likely involved in inhibiting the affective dimension of pain) significantly reduced postoperative pain and patient-controlled analgesia (PCA) use by 37% among 40 patients immediately following gastric- bypass surgery. However, methodological concerns surrounding these preliminary findings limit definitive conclusions about the effectiveness of TMS in controlling post-operative pain. This R21 proposal will integrate more rigorous experimental conditions, a true double-masked methodology, and longer-term follow- up assessment. The data from this R21 will provide the information needed for launching a definitive larger- scale investigation into potential clinical applications and mechanisms of action of TMS in controlling post- operative pain. Using rigorous double-masked methods and building on preliminary pilot work, we propose (Aim1) to test whether repetitive transcranial magnetic stimulation over the left prefrontal cortex significantly reduces post-operative pain and PCA use following gastric-bypass surgery. We also propose (Aim2) to determine the effects of timing and dose of TMS on post-operative pain and PCA use. Lastly, (Aim3) we propose to determine the effects of TMS on post-surgical recovery time, clinical outcomes and healthcare costs at 1-month, 3-months and 6-months follow-up. 132 participants will be randomly assigned to receive 20 minutes of: active prefrontal TMS or sham prefrontal TMS 45-minutes after gastric-bypass surgery. Participants will then be re-randomized to receive a second treatment (either real or sham) 8 hours later. Participants' PCA usage will be tracked along with twice-daily visual analogue scale ratings of postoperative pain and mood. This design provides 4 conditions yielding information relevant to the effects of timing and dose of TMS on postoperative pain control and longer-term clinical outcomes. Results from this pilot will likely supply substantial information about the utility of cortical stimulation for pain postoperative control. PUBLIC HEALTH RELEVANCE: The proper control of acute and chronic pain is one of the most important areas of health care, and despite profound advances in neuroscience, opiate narcotics are heavily relied upon for postoperative pain control. There are many risks associated with opiate use including respiratory depression, nausea and vomiting, cough suppression, mental clouding, sedation and constipation, and many of these side-effects are particularly problematic in gastric-bypass surgery patients who tend to have respiratory problems (like obstructive sleep apnea), right ventricular dysfunction, pulmonary hypertension, and for whom post-operative vomiting could result in serious complications. Thus, new interventions that have the potential to reduce reliance on postoperative morphine in this patient population such as TMS need to be explored.