Sensing Evoked Compound Action Potentials from the Spinal Cord: Novel Preclinical and Clinical Considerations for the Pain Management Researcher and Clinician

PURPOSE: Spinal cord stimulation (SCS) is a drug-free treatment for chronic neuropathic pain. Recent SCS technology can record evoked compound action potentials (ECAPs) in the spinal cord during therapy and utilize features of the sensed ECAP to optimize the SCS. The purpose of this work is to characterize the relevant parameters that govern the integrity and morphology of acquired ECAPs, and the implications for pain management clinicians and researchers working with ECAPs. MATERIALS AND METHODS: Eight-contact percutaneous SCS leads were implanted into sheep, and a prototype ECAP-sensing system was used to record spinal cord activity across a range of electrode configurations, pulse widths, and stimulus amplitudes. Similar iterative testing was then completed in human subjects who were undergoing trials of commercial SCS systems. RESULTS: Longer pulse width stimulation results in a progressive increase in ECAP latency, a neurophysiologic effect that enables ECAP sensing with longer pulses despite more encroachment by stimulation artifact. ECAPs may manifest a polyphasic morphology—an effect not seen in all subjects studied—with longer pulse width stimulation; these later phases may be used to assess ECAP amplitude when earlier features are effaced by artifact. Triphasic stimulation limits artifact from spinal cord ECAPs at the expense of potentially higher activation thresholds. If applied, alternating polarity stimulation must account for the ECAP latency differences resulting from alternating sites of neural activation. CONCLUSION: Together, this information can allow the ECAP to be readily distinguished from the stimulation artifact, although movement may continue to be a confounder; caution is inculcated for ECAP signal processing techniques that rely on the stability of the artifact to avoid clinically misleading results. The promise of closed-loop, ECAP-servoed neuromodulation relies on accurate and proper sensing of the ECAP, while clearly elucidating the clinically relevant trade-offs and design choices made to enable these novel features.