Minimally Invasive Intercostal Nerve Block Device to Treat Severe Pain and Reduce Usage of Opiates

项目摘要 每年接受开胸手术的20万美国人中的大多数接受阿片类药物以减少术后 疼痛，因为临床医生几乎没有非上瘾的、经济有效的选择来控制严重的疼痛患者通常 手术后前两周的经验。控制开胸手术后的疼痛是使患者能够 深呼吸，(通过咳嗽)排出肺部分泌物，否则会显著增加患心脏病的风险。 肺炎和肺部塌陷、再次入院和发病率。最严重的疼痛与 开胸手术是沿着肋间神经传递的。但没有长期止痛剂或神经阻滞器 存在可以提供安全有效的长期减轻疼痛的方法。而药物鸡尾酒往往是暂时的 减少许多患者的疼痛，电刺激器可以部分缓解(充其量50%-75%的患者)， 需要普遍适用的非成瘾性疼痛治疗方法。一种可逆的、由患者控制的、非 令人上瘾的肋间神经阻滞装置将减少因开胸手术、肋骨骨折和疱疹而造成的痛苦 带状疱疹。 在这个一期项目中，我们将开发一种微创热神经阻滞装置，它可以控制 通过对介于室温和温热之间的一小段神经进行温和加温和降温的神经传导 水温。这一新的方法是基于这样一个发现：温暖和凉爽的温度 神经阻滞机制不同且相加，可通过循环实现中温神经阻滞 略高于和低于体温的神经组织。可逆性热神经阻滞代表一种 一种全新的止痛方法。 在完成了猫科动物的研究并与FDA会面后，Aim#1将完成最低限度的开发 侵入性热提示以便于植入，开发控制系统以安全地操作设备，以及 肋间神经痛(C纤维)信号阻断系统的功能评价 在麻醉的猫科动物和绵羊身上进行皮肤针刺。热尖将循环神经温度在15- 45oC，由包含加热器/冷却器、电子设备和电源的外部设备控制。我们会 证明一个微创的尖端可以阻止肋间疼痛，并在15oC和 45摄氏度，同时将周围组织保持在35-39摄氏度的范围内。在目标2中，我们将评估疗效和 根据FDA的建议，6只清醒绵羊连续神经阻滞21天的初步安全性。 治疗后，我们将监测神经功能的恢复，并在治疗后7天和90天进行神经病理学检查。 治疗。成功完成第一阶段将支持人类使用设备的开发，并由CRO牵头 第二阶段的临床前GLP安全性和有效性研究，这反过来将为IDE会议做准备 美国食品和药物管理局。

Project Summary Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves. But no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. While drug cocktails often temporarily reduce pain in many patients, and electrical stimulators provide partial relief (50-75% of patients at best), a universally applicable non-addictive pain treatment modality is needed. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, we will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain. Having completed work in felines and met with FDA, Aim #1 will complete the development of the minimally invasive thermal tips for ease of implantation, develop the control system to operate the device safely, and evaluate the functional performance of the system for blocking intercostal nerve pain (C-fiber) signals induced by skin pinprick in anesthetized felines and sheep. The thermal tip will cycle nerve temperatures between 15- 45oC as controlled by an external unit that contains a heater/cooler, electronics and power source. We will demonstrate that a minimally invasive tip can block intercostal pain and accurately hold the nerve at 15oC and 45oC while maintaining surrounding tissue in a range of 35-39oC. In Aim #2, we will evaluate efficacy and preliminary safety in 6 conscious sheep for up to 21 days of continuous nerve block as suggested by FDA. Post-therapy we will monitor nerve function recovery and neuropathology will be done at 7- and 90-days post treatment. Successful completion of Phase I will support development of a human-use device and CRO-led pre-clinical GLP safety and efficacy study in Phase II, which in turn will prepare us for an IDE meeting with FDA.