Spinal cord stimulation (SCS) reduces chronic pain. Conventional (40-60 Hz) SCS engages spinal inhibitory mechanisms by activating low-threshold mechanoreceptive afferents with axons in the dorsal columns (DCs). But activating DC axons typically causes a buzzing sensation (paresthesia) that can be uncomfortable. Kilohertz-frequency (1-10 kHz) SCS produces analgesia without paresthesia and is thought, therefore, not to activate DC axons, leaving its mechanism unclear. Here we show in rats that kilohertz-frequency SCS activates DC axons but causes them to spike less synchronously than conventional SCS. Spikes desynchronize because axons entrain irregularly when stimulated at intervals shorter than their refractory period, a phenomenon we call overdrive desynchronization. Effects of overdrive desynchronization on evoked compound action potentials were verified in simulations, rats, pigs, and a chronic pain patient. Whereas synchronous spiking in DC axons is necessary for paresthesia, asynchronous spiking is sufficient to produce analgesia. Asynchronous activation of DC axons thus produces paresthesia-free analgesia.
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.
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