Focused Ultrasound Improves Spasticity After Spinal Cord Injury in Mouse Models Non-invasively and Reversibly

Introduction: Spinal cord injury (SCI) affects millions worldwide and is frequently accompanied by disabling muscle spasticity, chronic pain, and paralysis. Current treatments—including intrathecal baclofen pumps and epidural spinal cord stimulation—require invasive procedures and are associated with surgical risk, hardware complications, and substantial healthcare costs. Focused ultrasound (FUS) has recently emerged as a non-invasive neuromodulatory technology with the potential to influence neuronal activity reversibly and safely. Here, we present proof-of-concept evidence that FUS applied to the spinal cord can reduce spasticity in mouse models of SCI without causing tissue damage.

Methods: Adult C57BL/6J mice underwent complete spinal cord transection at the sacral level (S2), a model that reliably produces chronic tail spasticity without impairing hindlimb or autonomic function. A custom-designed ultrasound transducer was used to deliver FUS to the sacral spinal cord (200 ms burst duration; fundamental frequency 1 MHz; acoustic pressure 0.13 MPa; acoustic intensity 4.79 W/cm²). Tail position and movement were assessed before, during, and after ultrasound using an automated motion tracking system. In a separate cohort of wild-type mice, we assessed h-reflex modulation by applying FUS to the lumbar spinal cord while recording electrophysiologic responses from the hind paw. Tissue was harvested post-stimulation for immunohistochemistry with NeuN, ChAT, GFAP, and IBA1 to assess for neuronal, astrocytic, and microglial integrity.

Results: FUS suppressed the h-reflex amplitude by approximately 90% (p < 0.01), with responses returning to baseline within 2 minutes of stimulation cessation, indicating a reversible neuromodulatory effect. In the chronic S2 SCI model, FUS reduced tail spasm severity by ~35% and spasm frequency by ~30% (p < 0.05), as measured by decreased curvature and reduced involuntary tail movement. Immunohistochemical analysis revealed no evidence of neuronal loss, astrogliosis, or microglial activation, suggesting that FUS was well-tolerated and did not induce tissue damage.

Conclusion: This study demonstrates that FUS can modulate spinal reflex circuits to reduce spasticity in a fully non-invasive and reversible manner. The absence of detectable histologic injury and the rapid, reproducible behavioral improvements support the therapeutic potential of FUS as a novel alternative to invasive neuromodulation. This approach may ultimately transform the management of spasticity in SCI, offering improved safety, accessibility, and quality of life to patients suffering from SCI.