The Effect of Spinal Cord Stimulation Frequency on the Neural Response and Perceived Sensation in Patients With Chronic Pain

Abstract

Background: The effect of spinal cord stimulation (SCS) amplitude on the activation of dorsal column fibres has been widely studied through the recording of Evoked Compound Action Potentials (ECAPs), the sum of all action potentials elicited by an electrical stimulus applied to the fibres. ECAP amplitude grows linearly with stimulus current after a threshold, and a larger ECAP results in a stronger stimulus sensation for patients. This study investigates the effect of stimulus frequency on both the ECAP amplitude as well as the perceived stimulus sensation in patients undergoing SCS therapy for chronic back and/or leg pain.

Methods: Patients suffering with chronic neuropathic lower-back and/or lower-limb pain undergoing an epidural SCS trial were recruited. Patients were implanted according to standard practice, having two 8-contact leads (8 mm inter-electrode spacing) which overlapped 2-4 contacts around the T9/T10 interspace. Both lead together thus spanning about three vertebral levels. Neurophysiological recordings were taken during the patient's trial phase at two routine follow-ups using a custom external stimulator capable of recording ECAPs in real-time from all non-stimulating contacts. Stimulation was performed at various vertebral levels, varying the frequency (ranging from 2 to 455 Hz) while all other stimulating variables were kept constant. During the experiments subjects were asked to rate the stimulation-induced sensation (paraesthesia) on a scale from 0 to 10.

Results: Frequency response curves showed an inverse relationship between stimulation sensation strength and ECAP amplitude, with higher frequencies generating smaller ECAPs but stronger stimulation-induced paraesthesia (at constant stimulation amplitude). Both relationships followed logarithmic trends against stimulus frequency meaning that the effects on ECAP amplitude and sensation are larger for smaller frequencies.

Conclusion: This work supports the hypothesis that SCS-induced paraesthesia is conveyed through both frequency coding and population coding, fitting known psychophysics of tactile sensory information processing. The inverse relationship between ECAP amplitude and sensation for increasing frequencies at fixed stimulus amplitude questions common assumptions of monotonic relationships between ECAP amplitude and sensation strength.

Keywords: evoked compound action potential (ECAP); neural stimulation; spinal cord stimulation; stimulation frequency; stimulation sensation.

FIGURE 1

Activation plot example from Patient 13. The amplitude of the ECAP is calculated as the peak-to-peak amplitude of the first negative lobe and second positive lobe of the ECAP (dashed black line of the example ECAP shown in the figure inset). The ECAP amplitude increases linearly with stimulus current after reaching an activation threshold. Likewise, the sensation perceived also increases in strength from a threshold which normally is close to the activation threshold. Note that perception thresholds and ECAP thresholds can differ to a relatively small degree. Noise and the ability to record single fibre action potentials reliably is one factor, a potential psychophysical element cannot be ruled out. Sensation threshold was reached at 7.8 mA, a comfortable stimulation level was reached at 12.8 mA and the stimulus sensation was deemed maximal (starting to be uncomfortably strong) at 17 mA. Note that the threshold and slope of the activation plot for a particular patient with a fixed stimulating configuration varies with posture and other physiological changes (Parker et al., 2012, 2013; Mekhail et al., 2019; Russo et al., 2020).

FIGURE 2

Evoked Compound Action Potential in Patient 13 at 5 and 250 Hz, 7.9 mA stimulus current and 100 us pulse width. The frequency sweep was started at 5 Hz and increased up to 250 Hz before the stimulus became uncomfortable. The patient reported a sensation of 2/10 at 5 Hz and 9/10 at 250 Hz. The voltage between 0 ms (time reference that marks the start of the stimulating pulse) and 1 ms is 0 uV. This “blanking period” is due to the neural amplifiers of the recording system being blanked to avoid saturation while the stimulation pulse is delivered.

FIGURE 3

Normalised ECAP amplitude against stimulus frequency for all available data (grey dots) and the resulting average (black diamonds). Data from 16 patients and 22 frequency sweeps. A logarithmic fit was added to the average ECAP amplitudes.

FIGURE 4

Normalised sensation of all patients versus stimulus frequency (grey dots) (a total of 18 sweeps across 13 patients). Fewer data points are available at high stimulus frequencies as the stimulus sensation often became too strong for the patients at the given stimulus amplitude used. A logarithmic fit was added (solid line).