Preclinical Insights Into the Effects of Frequency and Pulse Width on Evoked Compound Action Potential Morphology...

High-frequency spinal cord stimulation (SCS) at 1000 Hz was shown to reduce evoked compound action potential (ECAP) amplitude, likely owing to asynchronous firing of dorsal column (DC) axons. To investigate the relationship between SCS parameters and DC axon activation, we analyzed ECAP morphology across different stimulation frequencies and pulse widths (PWs).

Adult male Sprague-Dawley rats (200-400 g) were implanted with an epidural lead. To study SCS frequency effects, baseline recordings were taken at 2 Hz, followed by tests at 50, 200, 500, and 1000 Hz, with 2 Hz recovery periods; 200 Hz also was applied in a pig with an epidurally implanted lead. PW effects were assessed in rats by increasing the PW from 50 to 1000 μs, in 50 μs increments per minute.

In contrast to 50 Hz, SCS at 200, 500, and 1000 Hz reduced ECAP amplitude and increased peak latencies and ECAP width. Conduction velocity (CV) was reduced at 500 and 1000 Hz. Recovery intervals at 2 Hz, after 200, 500, and 1000 Hz, showed a gradual return to baseline values for ECAP morphology parameters. Similar effects occurred in the pig. Increasing PW prolonged peak latencies, with ECAP amplitudes decreasing from 200 to 250 μs.

DC axon responses to SCS at increasing frequencies or PWs depend on their recovery state, as reflected in changes to ECAP morphology and CV. These effects may result from desynchronization, demyelination, or differences within fiber recruitment. Further investigation into these mechanisms can improve the efficacy of SCS therapy.