Gillespie Erica, Bouchal Elise, Elliott Trish, Pilitsis Julie G
Department of Neurosurgery, University of Arizona College of Medicine, Tucson, Arizona, USA.
Neurosurgery. 2025 Jul 17. doi: 10.1227/neu.0000000000003595.
The blood-brain barrier (BBB) presents a major challenge in administering pharmacological therapy for neurological disorders such as chronic pain. Focused ultrasound (FUS)-mediated BBB opening (BBBO) presents an alternative means of drug delivery. We examine potential candidate drugs and particle technology for use in FUS-mediated BBBO for treatment of pain. In this scoping review, we searched Pubmed and Embase databases for articles discussing FUS and pain. Using the Rayyan platform, we identified 705 articles and 376 were identified for abstract review, ultimately resulting in text review of 95. This scoping review was designed to address the following: (1) What are the limitations of chronic pain treatments in BBB penetration? and (2) What advancements in particles are likely to be used in FUS and BBBO for chronic pain? Despite interest in FUS-mediated BBBO for drug delivery in central nervous system disorders, no human studies have been conducted to assess its efficacy for the treatment of chronic pain. Preclinical work shows that many receptor agonists/antagonists reduce allodynia and hyperalgesia when administered directly to the brain, but not peripherally. Recent advances in particle and FUS technology allows precise targeting of specific brain regions and may hinder efflux and degradation of compounds at target. In combination with advancements in particle and FUS technology, drugs for treatment of chronic pain have been successful in preclinical models. Care must be chosen for selecting parameters, drugs, and particles for initial clinical studies to move the field forward successfully.
血脑屏障（BBB）对诸如慢性疼痛等神经疾病的药物治疗构成了重大挑战。聚焦超声（FUS）介导的血脑屏障开放（BBBO）提供了一种药物递送的替代方法。我们研究了用于FUS介导的BBBO治疗疼痛的潜在候选药物和颗粒技术。在这项范围综述中，我们在PubMed和Embase数据库中搜索了讨论FUS和疼痛的文章。使用Rayyan平台，我们识别出705篇文章，其中376篇被确定进行摘要审查，最终对95篇进行了全文审查。本范围综述旨在解决以下问题：（1）慢性疼痛治疗在血脑屏障穿透方面的局限性有哪些？（2）在FUS和BBBO用于慢性疼痛治疗中，颗粒技术可能会有哪些进展？尽管人们对FUS介导的BBBO用于中枢神经系统疾病的药物递送感兴趣，但尚未进行人体研究来评估其治疗慢性疼痛的疗效。临床前研究表明，许多受体激动剂/拮抗剂直接注入大脑时可减轻异常性疼痛和痛觉过敏，但外周给药则无效。颗粒和FUS技术的最新进展使得能够精确靶向特定脑区，并且可能会阻碍化合物在靶点处的外排和降解。结合颗粒和FUS技术的进展，治疗慢性疼痛的药物在临床前模型中已取得成功。在为初始临床研究选择参数、药物和颗粒时必须谨慎，以推动该领域的成功发展。
