Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement

Abstract

We acknowledge the Duke Compute Cluster for their assistance with our simulations. We thank Danielle Degoski for her assistance with experiments. Conflict of InterestA. No (State 'Authors report no conflict of interest') B. Yes (Please explain) T.Z. and R.E. are employees of Boston Scientific Corporation. J.E.G, N.D.T, T.Z. and W.M.G. have received royalty payments from Boston Scientific Corporation for licensed I.P. W.M.G received compensation from Boston Scientific as a member of the Neuromodulation Scientific Advisory Board. T.Z. and R.E. own Boston Scientific stock and R.E owns stock in NeuroPace.

Paresthesia during spinal cord stimulation depends on synchrony of dorsal column axon activation

“…Simulating the same model axons with different noise confirmed that uncorrelated noise and cellular heterogeneity are each sufficient to desynchronize spiking evoked by kf-SCS, yet neither desynchronizes the spiking evoked by c-SCS ( Supplementary Figure 9 ). Gilbert et al recently showed that pulses with perithreshold amplitude evoke spikes intermittently, causing desynchronization even at low frequencies 35 . Indeed, some perithreshold pulses can be rendered subthreshold by noise alone, without requiring spike-induced fluctuations in excitability (although such fluctuations expand the pulse amplitude range over which desynchronization occurs, abrogating the need to titrate pulse amplitude).…”

“…clinically), the charge per pulse is reduced as SCS frequency is increased, which further reduces the likelihood of paresthesia. Recent work showed that low-frequency (<100 Hz), small-amplitude pulses produce pain relief without paresthesia 66 by activating DC axons in a sparse, irregular pattern which engages spinal inhibition 35 . This argues that high-rate and/or low-amplitude SCS achieves paresthesia-free pain relief through asynchronous activation of DC axons.…”

Evoked compound action potentials during spinal cord stimulation: effects of posture and pulse width on signal features and neural activation within the spinal cord

“…Clinically, these results suggest that system operation at a lower target ECAP amplitude, such as near ET (which closely tracks PT)-an approach employed with some contemporary SCS therapies [37], and potentially enhanced further with closedloop control using ECAPs [8]-would provide more consistent dosing in the spinal cord and better approximate perceptual and electrophysiologic equivalence over posture and activity. Furthermore, it may be an option for patients that prefer paresthesiafree stimulation and help avoid complications associated with SCS-induced paresthesia, which can disturb sleep, or be experienced as excessive or uncomfortable [38,39].…”

Characterization and applications of evoked responses during epidural electrical stimulation

“…Despite this clinical adoption, the local neural substrates responsible for the therapeutic effects of EES, and consequently the mechanisms of action to control pain, are poorly understood. Activation of the large-diameter fibers in the dorsal columns is thought to inhibit pain transmission via gating within the dorsal horn (Zhang et al 2014 ; Yang et al 2011 ) however, several studies suggest that additional segmental and supraspinal mechanisms are involved in EES-induced analgesia (Gilbert et al 2022 ). Variations in the effect of EES to control pain can be attributed to multiple factors, such as initial placement or later migration of the electrode contacts, patient position, and the functional state of the neuronal circuitry (Mekhail et al 2022 ; Pahapill et al 2020 ; Dombovy-Johnson et al 2022 ).…”