Repeated epidural stimulation modulates cervical spinal cord excitability in healthy adult rats

Spinal evoked motor responses (SEMR) are utilized in longitudinal pre-clinical and human studies to reflect the in-vivo physiological changes in neural networks secondary to a spinal cord injury (SCI) or neuro-rehabilitative treatments utilizing epidural stimulation (ES). However, it remains unknown whether the repeated ES exposure during SEMR testing itself modulates spinal cord physiology and accompanying SEMR characteristics. To answer this, ES was delivered to the cervical spinal cord using standard stimulation paradigms during multiple SEMR data acquisition sessions (~ 17 h spanning across 100 days) in ten healthy adult rats. Cervical SEMR at rest and forelimb muscle activity during reaching and grasping task were collected before and after 100 days. We noted a persistent increase in SEMR activity relative to baseline, with prominent changes in the mono and poly-synaptic components of SEMR. The findings indicate increased spinal cord excitability. Increased spinal cord excitability translated into increased forelimb muscle activation during the reaching and grasping task. For the majority of SEMR and muscle activity increase, effect size was large or very large. Cervical SEMR are amenable to modulation by routine ES testing protocols, with prominent changes in the mono and poly-synaptic components of SEMR. Since repeated stimulation during multiple testing alone increases cord excitability, we recommend (1) SEMR may be used with caution to infer the physiological status of the spinal circuitry (2) utilizing appropriate control groups and motor behavioral correlates for meaningful functional interpretation in longitudinal neuromodulation studies involving multiple SEMR testing sessions following a SCI.