Focused Ultrasound-Induced Peripheral Nerve Blockade: Duration of Changes to Thermal Withdrawal Latency and Nerve Structure After Focused Ultrasound Application to the Sciatic Nerve in a Rat Model of Acute Pain

Focused ultrasound (FUS) holds potential to inhibit peripheral nerves to manage pain. We previously found FUS parameters resulting in changes to nerve structure and reversible increased mechanical withdrawal threshold as well as reversible inhibition of motor and non-pain sensory fibers. However, as behaviors were only followed for 4 weeks and structure for 2 weeks, the duration of increased thermal withdrawal latency and changes to nerve structure were undetermined. We investigated the duration of increased thermal withdrawal latency and nerve structure alterations after FUS application in an acute pain model. FUS was applied directly to the rat sciatic nerve prior to hindpaw (HP) incision; animal behaviors (thermal and mechanical nociceptive thresholds, HP extension and flexion) were assessed for 12 weeks and nerve structure was assessed for 28 weeks. The primary outcome was the change in HP thermal withdrawal latency. Secondary outcomes were the changes to sciatic nerve structure and HP mechanical withdrawal threshold, extension, and flexion. Compared with controls, after FUS application, animals had increased thermal nociceptive thresholds until week 9, increased mechanical nociceptive thresholds until week 2, decreased HP motor response until week 3.5, and decreased HP plantar sensation until week 4. Nerve ultrastructure changes may have persisted until week 24. In this new longer-term follow-up study, after invasive FUS application to the sciatic nerve in a rodent model of acute incisional pain, we determined the duration of changes to thermal hyperalgesia, mechanical hyperalgesia, motor, and non-pain sensory responses, and changes to nerve structure.