Remote Ischemic Conditioning Modulates Spinal Reflex Excitability in Healthy Young Adults: A Pilot Randomized Controlled Trial

Background: Remote ischemic conditioning (RIC), involving transient and sublethal bouts of ischemia and reperfusion, promotes neuroplasticity and motor learning. Although early clinical studies suggest supraspinal and muscular mechanisms underlying RIC, its influence on spinal reflex excitability - a key substrate for motor learning - remains poorly understood. Balance training alone is known to modulate spinal excitability, but whether RIC can enhance this training-induced adaptation has not been tested. Objective: This prospective single-blind, pilot randomized controlled trial (RCT) explored the preliminary effects of pairing RIC with balance training on spinal reflex excitability and balance performance in healthy young adults and generated estimates of variability to inform a future definitive randomized trial. Methods: Twenty-six participants aged between 18-40 years were randomized to RIC or sham groups at university-based research setting between March and August 2025. The intervention included five cycles of 5-minute cuff inflation (RIC: 200 mmHg; sham: 25 mmHg) and 5-minute deflation on the dominant thigh, followed by balance training on a stability platform (15 trials/day) for five consecutive days. Pre- and post-intervention assessments included Hoffmann's reflex (H-reflex) parameters - Hmax (peak H-reflex amplitude reflecting motor neuron recruitment via Ia afferent input), H/M ratio (Hmax normalized to maximal M-wave amplitude), Hslp/Mslp ratio (relative slope of the H-reflex and M-wave recruitment curves), and H-reflex threshold (minimum stimulus intensity eliciting a response) - used to index spinal motor neuron pool excitability, as well as balance performance, quantified as center time (the duration participants maintained a stability platform within a set horizontal threshold). Independent sample and Mann-Whitney U tests analyzed the differences in the change scores (RIC vs Sham) for H-reflex and balance outcomes respectively. Results: The RIC group showed directionally greater reduction in the Hslp/ Mslp ratio (p = 0.02) and greater improvement in balance performance (p = 0.02) compared to sham group. No significant between-group differences were observed for Hmax, H/M ratio, or H-reflex threshold; however, the direction of changes in Hmax was consistent with reduced spinal reflex excitability following RIC. These findings potentially suggest that RIC could augment the neuroplastic adaptations typically induced by balance training. Conclusion: This pilot study provides preliminary evidence that RIC paired with balance training may influence selected spinal neurophysiological responses and improve balance performance in healthy adults. The potential convergence of neurophysiological and behavioral adaptations observed in this pilot study may suggest a role for RIC as a physiological primer for sensorimotor learning. Moreover, these findings establish a foundation for future large-scale trials incorporating cortical and presynaptic inhibitory measures to elucidate mechanisms and clinical applicability in neurological populations. Keywords: H-reflex, spinal modulation, remote ischemic conditioning, motor learning, neuroplasticity, randomized controlled trials.

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Journal
medRxiv
Published
2026-10-28
DOI
https://doi.org/10.64898/2026.10.28.26362269
Primary Topic
Spinal Cord Injury Research
Type
preprint
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preprint

Remote Ischemic Conditioning Modulates Spinal Reflex Excitability in Healthy Young Adults: A Pilot Randomized Controlled Trial

John D. Willson, Erzsebet M. Szatmari, Shailesh Gardas, Max J. Kurz et al.
medRxiv
Spinal Cord Injury Research
preprint

Remote Ischemic Conditioning Modulates Spinal Reflex Excitability in Healthy Young Adults: A Pilot Randomized Controlled Trial

John D. Willson, Erzsebet M. Szatmari, Shailesh Gardas, Max J. Kurz, Linda E. May, Swati M. Surkar, Chia-Cheng Lin, Sarah Baker
preprint en

Abstract

Background: Remote ischemic conditioning (RIC), involving transient and sublethal bouts of ischemia and reperfusion, promotes neuroplasticity and motor learning. Although early clinical studies suggest supraspinal and muscular mechanisms underlying RIC, its influence on spinal reflex excitability - a key substrate for motor learning - remains poorly understood. Balance training alone is known to modulate spinal excitability, but whether RIC can enhance this training-induced adaptation has not been tested. Objective: This prospective single-blind, pilot randomized controlled trial (RCT) explored the preliminary effects of pairing RIC with balance training on spinal reflex excitability and balance performance in healthy young adults and generated estimates of variability to inform a future definitive randomized trial. Methods: Twenty-six participants aged between 18-40 years were randomized to RIC or sham groups at university-based research setting between March and August 2025. The intervention included five cycles of 5-minute cuff inflation (RIC: 200 mmHg; sham: 25 mmHg) and 5-minute deflation on the dominant thigh, followed by balance training on a stability platform (15 trials/day) for five consecutive days. Pre- and post-intervention assessments included Hoffmann's reflex (H-reflex) parameters - Hmax (peak H-reflex amplitude reflecting motor neuron recruitment via Ia afferent input), H/M ratio (Hmax normalized to maximal M-wave amplitude), Hslp/Mslp ratio (relative slope of the H-reflex and M-wave recruitment curves), and H-reflex threshold (minimum stimulus intensity eliciting a response) - used to index spinal motor neuron pool excitability, as well as balance performance, quantified as center time (the duration participants maintained a stability platform within a set horizontal threshold). Independent sample and Mann-Whitney U tests analyzed the differences in the change scores (RIC vs Sham) for H-reflex and balance outcomes respectively. Results: The RIC group showed directionally greater reduction in the Hslp/ Mslp ratio (p = 0.02) and greater improvement in balance performance (p = 0.02) compared to sham group. No significant between-group differences were observed for Hmax, H/M ratio, or H-reflex threshold; however, the direction of changes in Hmax was consistent with reduced spinal reflex excitability following RIC. These findings potentially suggest that RIC could augment the neuroplastic adaptations typically induced by balance training. Conclusion: This pilot study provides preliminary evidence that RIC paired with balance training may influence selected spinal neurophysiological responses and improve balance performance in healthy adults. The potential convergence of neurophysiological and behavioral adaptations observed in this pilot study may suggest a role for RIC as a physiological primer for sensorimotor learning. Moreover, these findings establish a foundation for future large-scale trials incorporating cortical and presynaptic inhibitory measures to elucidate mechanisms and clinical applicability in neurological populations. Keywords: H-reflex, spinal modulation, remote ischemic conditioning, motor learning, neuroplasticity, randomized controlled trials.

medRxiv
East Carolina University (US), Boys Town National Research Hospital (US)
Good health and well-being
Spinal Cord Injury Research
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