Electrophysiologic Characteristics of Epidural Spinal Signals in Preclinical Models of Spinal Cord Stimulation

Epidural stimulation of the spinal cord evokes distinct electrophysiologic responses that can be recorded epidurally. Here, we characterized evoked compound action potentials (ECAPs), doublets (secondary or tertiary ECAPs, probably of different physiologic origin from primary ECAPs), evoked synaptic activity potentials (ESAPs), and electromyographic (EMG) signals in preclinical models. Our objective was to clarify the features and distinct physiologic origins of these signals, to advance mechanistic studies and support clinical applications of spinal cord stimulation (SCS) therapy.

Adult male Sprague-Dawley rats (300-440 g) were implanted with two epidural leads (caudal and rostral; each with eight electrodes) and received monopolar, biphasic stimulation (200-μs pulse width) at 2 and 50 Hz, with current increased stepwise to motor threshold. Rhesus macaques (11.5 and 10.2 kg) were implanted with a single 12-electrode epidural lead and stimulated using either tripolar, triphasic pulses at 10 Hz (100 μs) or tripolar, biphasic pulses at 3 Hz (80 μs) up to 3 × ECAP threshold. Recordings were taken from nonstimulating electrodes.

ECAPs and EMG signals were recorded across multiple spinal segments in both rats (L1-T7) and macaques (L2-T11). Doublets presented as complex waveforms with multiple negative peaks, two in rats and three in macaques, likely representing distinct ECAPs at T11-T6 in a rat and L1-T11 in macaques. ESAPs, detectable in rats, showed anatomical specificity over the L1/T13 vertebrae, with peak responses at L1. Signal analysis included activation thresholds, amplitudes, latencies, and conduction velocities.

This study outlines electrophysiologic signals evoked by SCS in terms of their waveform, recruitment thresholds, and putative physiologic origins. We propose that to some extent, these signals reflect different aspects of spinal processing and may serve as biomarkers of dysregulated nociceptive pathways, and as indicators of SCS efficacy or potential side effects.