Peripheral Nerve Blocks with Multimodal Analgesics

使用多模式镇痛药进行周围神经阻滞

• 批准号: 7512087
• 负责人: BRIAN ALAN WILLIAMS
• 金额: $ 15.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7512087
• 关键词: Absence of pain sensation; Address; Adverse effects; Afferent Neurons; Analgesics; Anesthesiology; Animal Model; Basic Science; Blinded; Bupivacaine; Buprenorphine; Cell Death; Clinical; Clinical Research; Clonidine; Dependence; Development; Dexamethasone; Dose; Drug Combinations; Drug vehicle; End Point; Gold; Histologic; Hour; In Vitro; Injection of therapeutic agent; Injury; Joints; K-Series Research Career Programs; Lead; Limb structure; Local Anesthetics; Mechanics; Methods; Motor; Myalgia; Narcotic Analgesics; Nerve; Nerve Block; Nociception; Operative Surgical Procedures; Opioid; Opioid Analgesics; Orthopedic Surgery procedures; Pain; Pain management; Patients; Peripheral Nerves; Pharmaceutical Preparations; Postoperative Period; Public Health; Rate; Rattus; Risk; Solutions; Spinal Ganglia; Standards of Weights and Measures; Testing; Time; Toxicology; Training; Week; Withdrawal; bone; day; desire; experience; falls; improved; in vivo; neurotoxic; neurotoxicity; perineural; prevent; ropivacaine; sciatic nerve

DESCRIPTION (provided by applicant): In the subspecialty of anesthesiology for orthopedic surgery, the past 12 years have provided remarkable advances in opioid-sparing analgesia via the regular use of peripheral nerve blocks. However, single injection nerve blocks with local anesthetics provide only 12 hours of analgesia, leading to little opioid sparing. As a result, continuous peripheral nerve blocks have evolved into a new "gold standard" in opioidsparing analgesia for 2-4 days after surgery. However, continuous nerve blocks with local anesthetics are expensive, labor-intensive, require subspecialty training, and have unique complications (e.g., risk of falling due to motor block). These barriers seem likely to prevent continuous nerve blocks from having an impact on public health beyond the status of a subspecialty niche. The next breakthrough in postoperative nerve block analgesia will involve single-injections that provide sustained analgesia (24-48 hours) without producing unwanted motor block or nerve damage. Sustained-release local anesthetics (e.g., microcapsulated bupivacaine) have not been successful in meeting these objectives. By combining drugs of varying mechanisms, a "multimodal" analgesic may prove to reduce or eliminate the need for postoperative opioid analgesia; if such a drug combination is both safe to the peripheral nerve and efficacious, then an important public health advance is possible. The objective of this Career Development Award is to capitalize on previous clinical research experience with continuous nerve blocks, and to supplement this prior clinical experience with 2 years of additional formal training in the basic science of nociception, analgesia, and peripheral nerve toxicology. The candidate aims to develop appropriate animal models addressing these questions, and thus accelerate scientific progress on the development of a multimodal analgesic nerve block. Such a block would further advance opioid-sparing analgesia, and aim to reduce patient dependence on opioid analgesics as the primary mechanism of analgesia in the first week(s) after orthopedic surgery. After orthopedic surgery (surgery on the bones, joints, and muscles), pain is commonly rated as "moderate" to "severe." The most common method to treat pain after surgery is with opioid analgesics (narcotics), which can both have many side effects and also be addictive. Continuous nerve blocks have helped to reduce opioid requirements, but are technically complicated and subspecialized, while local anesthetics can produce unwanted motor block that may lead to the injury of an insensate extremity. This application is presented to develop a method to improve single-injection nerve blocks, in order to provide (i) sustained pain relief after surgery, (ii) reduced motor block, and (iii) reduced opioid requirements.

描述（由申请人提供）：在骨科手术麻醉学亚专业中，过去 12 年通过定期使用周围神经阻滞在节省阿片类药物镇痛方面取得了显着进展。然而，单次注射局麻药神经阻滞只能提供 12 小时的镇痛效果，导致阿片类药物的节省很少。因此，连续周围神经阻滞已发展成为术后 2-4 天阿片类药物镇痛的新“金标准”。然而，使用局部麻醉剂进行连续神经阻滞是昂贵的、劳动密集型的、需要专科培训，并且具有独特的并发症（例如，由于运动阻滞而导致跌倒的风险）。这些障碍似乎可能会阻止持续的神经阻滞对公共健康产生超出亚专业地位的影响。术后神经阻滞镇痛的下一个突破将涉及单次注射，提供持续镇痛（24-48 小时），而不会产生不必要的运动阻滞或神经损伤。缓释局部麻醉剂（例如微囊布比卡因）尚未成功实现这些目标。通过结合不同机制的药物，“多模式”镇痛药可能会减少或消除术后阿片类镇痛的需要；如果这种药物组合对周围神经既安全又有效，那么就有可能在公共卫生方面取得重大进展。该职业发展奖的目的是利用先前连续神经阻滞的临床研究经验，并通过 2 年伤害感受、镇痛和周围神经毒理学基础科学方面的额外正式培训来补充先前的临床经验。该候选人旨在开发适当的动物模型来解决这些问题，从而加速多模式镇痛神经阻滞开发的科学进展。这种阻断将进一步推进阿片类镇痛，并旨在减少患者对阿片类镇痛药的依赖，作为骨科手术后第一周镇痛的主要机制。骨科手术（骨骼、关节和肌肉手术）后，疼痛通常被评定为“中度”至“重度”。治疗手术后疼痛的最常见方法是使用阿片类镇痛药（麻醉药），它不仅有许多副作用，而且还会让人上瘾。连续神经阻滞有助于减少阿片类药物的需求，但技术复杂且专业化，而局部麻醉剂会产生不必要的运动阻滞，可能导致无知觉的肢体受伤。本申请旨在开发一种改进单次注射神经阻滞的方法，以提供（i）术后持续疼痛缓解，（ii）减少运动阻滞，以及（iii）减少阿片类药物需求。