Development of A Focused Ultrasound Device for Noninvasive, Peripheral Nerve Blockade to Manage Acute Pain

Abstract
The US opioid epidemic developed in large part as a result of the widespread prescription of opioids for
the treatment of acute pain. Moderate and severe acute pain are prevalent in many healthcare settings
and associated with adverse outcomes (e.g., increased risk of myocardial ischemia, worsened quality
of life, increased healthcare costs). Current acute pain management strategies (systemic analgesics
and peripheral nerve blocks (PNBs)) insufficiently treat pain. Systemic analgesics, e.g., opioids, are
inadequate for controlling acute pain (as they primarily block C nociceptive fibers, not A-delta
nociceptive fibers) and have many harmful side effects, frequently resulting in addiction. Current PNB
techniques, via the injection of local anesthetics at peripheral nerves, improve acute pain outcomes for
some patients but have significant shortcomings limiting use (e.g, they are invasive, increase care
complexity, and only manage acute pain for a limited amount of time). FUS-induced PNB is a ground-
breaking technology/technique that may serve as an alternative to traditional local anesthetic-based
PNB, preventing the need for opioids to manage acute pain, and reducing the risk of developing chronic
pain. This proposal outlines aims to translate FUS technology into a novel medical device for
noninvasive PNB to improve acute pain management leading to a dramatic paradigm shift in acute pain
treatment. Prior investigations support FUS’s potential for managing acute pain. Investigators have
found that application of FUS to peripheral nerves in ex vivo and in vivo animal models results in dose-
dependent reversible reduction in peripheral nerve compound action potential amplitude and a transient
increase in nociceptive thresholds in rodent neuropathic pain models with reversible effects on nerve
structure. In an in vivo rodent model of acute pain, we determined FUS parameters for reversible
blockade of peripheral nerve fibers. Further, we have demonstrated that FUS can be applied
transcutaneously to block peripheral nerve function. FUS-induced PNB as a novel clinical tool for
managing acute pain is held back by several addressable gaps in knowledge and need for
technological development: 1) An insufficient understanding of the optimal parameters for
transcutaneous (noninvasive) FUS application to peripheral nerves resulting in reversible blockade and
without adverse effects; 2) No available FUS device with the frequency and focal zone (high pressure
area) geometry required for application to non-human primate (NHP) and human peripheral nerves;
and 3) Absence of studies evaluating transcutaneous FUS application to peripheral nerves for
reversible PNB in a NHP model of acute pain. The present Aims will address the existing barriers
preventing clinical trials investigating FUS-induced PNB for acute pain management.

Grant Number: 1R18EB035005-01
NIH Institute/Center: NIH
Principal Investigator: Thomas Anderson