A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing

Background The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear. Methods We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The conditioning stimulation intensity was set at the lowest current that evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ- or C-compound action potential. Results Within 15 min of the dorsal column or root conditioning stimulation, the spontaneous activity rate of WDR neurons was significantly reduced in nerve-injured rats. Conditioning stimulation also significantly attenuated WDR neuronal responses to mechanical stimuli in nerve-injured rats and inhibited the C-component of the neuronal response to graded intracutaneous electrical stimuli applied to the receptive field in nerve-injured and sham-operated rats. It is noteworthy that dorsal column stimulation blocked windup of WDR neuronal response to repetitive intracutaneous electrical stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root stimulation inhibited windup only in sham-operated rats. Therefore, stimulation of putative spinal substrates at A-fiber intensities with parameters similar to those used by patients with spinal cord stimulators attenuated established WDR neuronal hyperexcitability in the neuropathic condition and counteracted activity-dependent increase in neuronal excitability (i.e., windup). Conclusions These results suggest a potential cellular mechanism underlying spinal cord stimulation-induced pain relief. This in vivo model allows the neurophysiologic basis for spinal cord stimulation-induced analgesia to be studied.

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The Evoked Compound Action Potential as a Predictor for Perception in Chronic Pain Patients: Tools for Automatic Spinal Cord Stimulator Programming and Control

Frontiers in Neuroscience ◽

10.3389/fnins.2021.673998 ◽

2021 ◽

Vol 15 ◽

Author(s):

Julie G. Pilitsis ◽

Krishnan V. Chakravarthy ◽

Andrew J. Will ◽

Karen C. Trutnau ◽

Kristin N. Hageman ◽

...

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Action Potential ◽

Pulse Width ◽

Growth Curves ◽

Compound Action Potential ◽

Novel Approach ◽

Technological Advances ◽

Evoked Compound Action Potential ◽

Compound Action

ObjectivesSpinal cord stimulation (SCS) is a drug free treatment for chronic pain. Recent technological advances have enabled sensing of the evoked compound action potential (ECAP), a biopotential that represents neural activity elicited from SCS. The amplitudes of many SCS paradigms – both sub- and supra-threshold – are programmed relative to the patient’s perception of SCS. The objective of this study, then, is to elucidate relationships between the ECAP and perception thresholds across posture and SCS pulse width. These relationships may be used for the automatic control and perceptually referenced programming of SCS systems.MethodsECAPs were acquired from 14 subjects across a range of postures and pulse widths with swept amplitude stimulation. Perception (PT) and discomfort (DT) thresholds were recorded. A stimulation artifact reduction scheme was employed, and growth curves were constructed from the sweeps. An estimate of the ECAP threshold (ET), was calculated from the growth curves using a novel approach. Relationships between ET, PT, and DT were assessed.ResultsETs were estimated from 112 separate growth curves. For the postures and pulse widths assessed, the ET tightly correlated with both PT (r = 0.93; p < 0.0001) and DT (r = 0.93; p < 0.0001). The median accuracy of ET as a predictor for PT across both posture and pulse width was 0.5 dB. Intra-subject, ECAP amplitudes at DT varied up to threefold across posture.ConclusionWe provide evidence that the ET varies across both different positions and varying pulse widths and suggest that this variance may be the result of postural dependence of the recording electrode-tissue spacing. ET-informed SCS holds promise as a tool for SCS parameter configuration and may offer more accuracy over alternative approaches for neural and perceptual control in closed loop SCS systems.

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Defining the Therapeutic Window (TW) for Spinal Cord Stimulation (SCS) Using Evoked Compound Action Potential (ECAP) Recordings: Results From the Evoke Study

Neurosurgery ◽

10.1093/neuros/nyz310_194 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Robert M Levy

Keyword(s):

Spinal Cord ◽

Spinal Cord Stimulation ◽

Closed Loop ◽

Compound Action Potential ◽

Open Loop ◽

Therapeutic Window ◽

Perception Threshold ◽

Electrical Field Strength ◽

Evoked Compound Action Potential

Abstract INTRODUCTION Spinal cord stimulation (SCS) is an established treatment for chronic pain; however, long-term success remains suboptimal. Current SCS therapies are fixed-output and do not account for large variation in electrical field strength due to changes in distance between the electrode and spinal cord (SC). METHODS In Avalon, 50 subjects were implanted and programmed in closed-loop; in Evoke, 134 subjects were randomized into open-loop (OL-SCS) or closed-loop (CL-SCS). ECAPs, a measure of SC activation, are recorded following each stimulation pulse in both groups. Each subject's therapeutic window (TW) is determined individually as the ECAP amplitude range between sensation perception threshold and discomfort. Without a measure of SC activation (eg, ECAPs), TW can only be based on perception of intensity; however, stimulation can produce variable SC activation (ECAP amplitude) as the electrode to SC distance varies with movement. RESULTS In the Evoke Study, each subjects' TW was determined in the clinic, along with the clinician prescribed level. There was no statistical difference between the 2 groups' TWs; however, CL-SCS subjects spent significantly more time in the TW despite having equivalent therapeutic ranges. Long-term data showed a similar percentage of stimuli in the TW (83%-97%). CONCLUSION TW can be individually defined by ECAP amplitudes (measure of SC activation), removing the need to rely on subjective reports of intensity, which can vary over time and with movement.

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