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

微创肋间神经阻滞装置治疗严重疼痛并减少阿片类药物的使用

• 批准号: 9908680
• 负责人: Stephen Popielarski
• 金额: $ 49.93万
• 依托单位: THERMAQUIL, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908680
• 关键词: Acute; Aftercare; American; Analgesics; Animals; Biological Models; Body Temperature; C Fiber; Cicatrix; Conscious; Coughing; Data; Development; Devices; Drug usage; Effectiveness; Electric Stimulation; Electrodes; Electronics; Evaluation; Exposure to; Family Felidae; Feasibility Studies; Female; Herpes zoster disease; Human; Implant; Liquid substance; Lung; Mechanics; Medical; Methods; Modality; Monitor; Morbidity - disease rate; Motor; Muscle; Nerve; Nerve Block; Nerve Pain; Nerve Tissue; Nervous System Physiology; Neural Conduction; Neurologic; Neurology; Operative Surgical Procedures; Opioid; Pain; Pain management; Patients; Performance; Pharmaceutical Preparations; Phase; Pneumonia; Positioning Attribute; Postoperative Pain; Power Sources; Preparation; Procedures; Property; Recommendation; Recovery; Recovery of Function; Risk; Safety; Sheep; Side; Signal Transduction; Silicones; Site; Skin; Small Business Technology Transfer Research; Suggestion; Surface; Surgical sutures; System; Temperature; Testing; Thoracotomy; Time; Tissues; Universities; Ventral thoracic nerve structure; Water; Work; base; clinical practice; cost; cost effective; dermatome; design; efficacy study; experience; hospital readmission; implantation; improved; in vivo evaluation; innovation; male; meetings; minimally invasive; neuropathology; neurotransmission; novel strategies; opioid use; pain patient; pain reduction; pain signal; performance tests; pre-clinical; preclinical study; relating to nervous system; rib bone structure; safety study; sample fixation; success; transmission process; warm temperature

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.

项目摘要 每年接受开胸手术的20万美国人中，大多数人接受阿片类药物，以减少术后并发症。 疼痛，因为临床医生很少有非成瘾性的，具有成本效益的选择，以控制严重的疼痛患者往往 在手术后的前两个星期。开胸术后疼痛的管理对于使患者能够 深呼吸并（通过咳嗽）清除肺部分泌物，否则会显著增加 肺炎和肺萎陷、再次入院和发病率。最严重的疼痛与 胸廓切开术是沿肋间神经沿着传递的。但没有长期止痛或神经阻滞装置 存在可以提供安全有效的长期疼痛减轻的药物。虽然药物鸡尾酒通常是暂时的， 减少许多患者的疼痛，电刺激器提供部分缓解（最多50 - 75%的患者）， 需要普遍适用的非成瘾性疼痛治疗方式。一种可逆的，病人控制的，非- 肋间神经阻滞装置可以减少开胸手术、肋骨骨折和疱疹带来的痛苦 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， 通过在室温和温热之间温和地加热和冷却短神经段来进行神经传导 水温这种新颖的方法是基于这样的发现，即温暖和凉爽的温度 神经阻滞的机制是不同的且可加性的，可以通过循环实现中温神经阻滞 神经组织的温度略高于和低于体温。可逆性热神经阻滞代表了 一种全新的疼痛管理方法 在完成猫的工作并与FDA会面后，目标1将完成最低限度的开发。 易于植入的侵入性热尖端，开发控制系统以安全操作器械，以及 评价系统阻断肋间神经疼痛（C纤维）信号的功能性能 通过麻醉猫和羊的皮肤针刺。热尖端会使神经温度在15- 45oC，由包含加热器/冷却器、电子设备和电源的外部装置控制。我们将 证明微创尖端可以阻断肋间疼痛，并将神经准确保持在15 ℃， 45 ℃，同时将周围组织保持在35 - 39 ℃的范围内。在目标2中，我们将评估疗效， FDA建议的6只清醒绵羊长达21天的连续神经阻滞的初步安全性。 治疗后，我们将监测神经功能恢复情况，并在治疗后7天和90天进行神经病理学检查 治疗第一阶段的成功完成将支持人类使用设备的开发， II期临床前GLP安全性和有效性研究，这反过来将为我们准备IDE会议， FDA.