Cervical Spinal Cord Modulation with Repeated Epidural Stimulation in Healthy Adult Rats

The effects of spinal epidural stimulation (ES) in regaining various physiological functions after a spinal cord injury (SCI) are well documented. Spinal evoked motor responses (SEMR) are commonly utilized experimental outcomes in longitudinal pre-clinical and human studies to reflect the in-vivo physiological changes in neural networks secondary to a neurological insult or neuro-rehabilitative treatments utilizing ES. However, it remains unknown if the repeated exposure to ES during SEMRs testing itself modulates the spinal cord physiology and hence the SEMRs characteristics. To address this issue, cervical ES was delivered to the healthy adult rats cervical cord using standard stimulation paradigms during multiple sessions ([~]17 hours that spanned across 100 days). Cervical SEMR and electromyography (EMG) activity from forelimb muscles during a reaching & grasping task were collected before and after 100 days. We noted persistent increase in the cervical SEMR and forelimb muscle activity during reaching & grasping task relative to baseline at the end of the stimulation period indicating increased spinal and cortical excitability. Findings from the present work suggests that cervical SEMRs are amenable to modulation by routine ES testing protocols, with prominent changes in the mono and poly synaptic component of evoked responses. Additionally, since multiple testing sessions of cervical ES alone increases the excitability of the intact spinal cord, we suggest that SEMR data be used with caution to infer the physiological status of the spinal circuitry in longitudinal studies involving multiple SEMR testing sessions. Our findings also recommend involving appropriate control groups, motor behavior correlates, and practicing caution while utilizing normalization methods to allow meaningful functional interpretation of SEMR profiles following a SCI.