A Scoping Review of Focused Ultrasound- Blood-Brain Barrier Opening for Treatment of Chronic Pain.

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.