Dynamic Stimulation Waveforms in Spinal Cord Stimulation Enhance Benefits of Variable Activation of Dorsal Columns

Introduction: Recent work has suggested that low rate static (tonic) sub-perception spinal cord stimulation (SCS) approaches engage dorsal column (DC) fibers variably and thereby enhance dorsal horn inhibition while mitigating undesired excitation [1,2], and opportunities exist to improve the approach by exploiting this mechanism. Dynamic stimulation is a new paradigm of (SCS) that, in contrast to static SCS, involves intentionally varying one or more stimulation parameters (e.g. amplitude, pulse width) over time and is potentially more effective than static SCS for relieving chronic pain [3]. One hypothesis for enhanced efficacy by dynamic SCS is the intentional and enhanced generation of variable activation of dorsal column (DC) fibers relative to static SCS. However, assessments and comparisons versus static SCS have not been previously performed.

Methods: In this modeling study, we simulated the responses of DC fibers to static and dynamic SCS and compared the resultant patterns of activation. We coupled extracellular voltages generated through finite element modeling of the human spinal cord [4] during monopolar, bipolar, and tripolar SCS configurations to biophysical models of mammalian axons and compared DC axonal activation patterns due to several dynamic SCS waveforms and pulse-rate matched static SCS controls. We further assessed whether varying activation, defined as SCS-evoked activity that did not occur with every pulse in the waveform, occurred over therapeutically relevant amplitudes (≤6mA), and we compared the sensitivity of the dosing windows over which varying activation occurred due to stimulation geometry, dCSF thickness, and fiber diameter.

Results: Single fiber varying activation occurred in response to dynamic SCS over clinically relevant paresthesia-free amplitudes) and multiple dCSF depths. In addition, consistent with our hypothesis, dynamic SCS substantially increased the proportion of fibers exhibiting varying activation: across all simulations, static stimulation was only able to variably activate up to 60% of fibers, with this maximum only at the population threshold amplitude, whereas dynamic SCS could variably activate up to 100% of fibers over a substantially larger dosage range. Such occurrence of varying activation was not restricted to any tested fiber diameters (8.0-11.5μm) or stimulation geometries.

Conclusion: Computational modeling predicts that dynamic SCS is a strategy to optimize SCS by deliberately enhancing variable DC activation shown previously[1, 2] to be beneficial for dispersing and reducing synaptic excitation of excitatory dorsal horn elements, while preserving dorsal horn inhibition. Further work to experimentally characterize and validate the effects of DC variable activation on dorsal horn pain processing is needed.