Noninvasive Diagnostic Ultrasound-Guided Focused Ultrasound Enables Selective, Reversible Inhibition of Peripheral...

Acute postoperative pain remains a major clinical therapeutic challenge. Current peripheral nerve blockade (PNB) techniques are effective for some patients but are limited by invasiveness, short duration, reliance on highly trained providers, and off-target motor and sensory effects. Focused ultrasound (FUS) is a novel neuromodulatory technology with the potential to achieve noninvasive, selective, reversible, and prolonged inhibition of peripheral nociceptive fibers to prevent and treat acute pain. We hypothesized that noninvasive transcutaneous targeting of the rat sciatic nerve using co-aligned diagnostic ultrasound (dUS) and FUS transducers could produce selective and reversible inhibition of nociceptive pain behaviors while preserving motor and non-nociceptive sensory functions.

In an in vivo rat hindpaw incisional (HPI) pain model, using a novel, transcutaneous dUS-guided FUS system, the sciatic nerve was located with dUS, and FUS energy was applied to it just prior to hindpaw incision. FUS parameters were iteratively adjusted to achieve reversible, selective inhibition of nociceptive behaviors without changing motor and non-pain sensory behaviors. Animals were randomized into six groups: No Intervention (Control), HPI Only (Disease Control), Sham FUS, FUS Only, FUS+HPI (Intervention), and LA+HPI (Positive Control). Primary outcomes were changes in nociceptive sensory functions, assessed by thermal and mechanical sensitivity. Secondary outcomes were changes in non-nociceptive sensory and motor functions, assessed by hindpaw flexion and extension reflexes.

Compared with the HPI Only group, the FUS+HPI group demonstrated (1) significant attenuation of hindpaw thermal hypersensitivity from day 0 - week 5.0 and week 8.0 - 16.0 (p < 0.05-0.001); (2) significant attenuation of mechanical hypersensitivity from day 0 until week 4.0 (p < 0.05-0.001); (3) no significant attenuation of flexion; and (4) no significant attenuation of extension.

Transcutaneous dUS-guided FUS enables selective, reversible inhibition of Aδ and C nociceptive fiber mediated behaviors while sparing Aα motor and Aβ sensory behaviors. FUS-induced PNB prevented both acute and persistent pain behaviors. These findings support FUS as a promising noninvasive peripheral nerve blockade strategy for acute pain management.