Absence of paresthesia during high-rate spinal cord stimulation reveals importance of synchrony for sensations evoked by electrical stimulation.

Autor:	Sagalajev B; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Zhang T; Boston Scientific Neuromodulation, Valencia, CA 25155, USA., Abdollahi N; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada., Yousefpour N; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada., Medlock L; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada., Al-Basha D; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Ribeiro-da-Silva A; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada., Esteller R; Boston Scientific Neuromodulation, Valencia, CA 25155, USA., Ratté S; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Prescott SA; Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: steve.prescott@sickkids.ca.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Feb 07; Vol. 112 (3), pp. 404-420.e6. Date of Electronic Publication: 2023 Nov 15.
DOI:	10.1016/j.neuron.2023.10.021
Abstrakt:	Electrically activating mechanoreceptive afferents inhibits pain. However, paresthesia evoked by spinal cord stimulation (SCS) at 40-60 Hz becomes uncomfortable at high pulse amplitudes, limiting SCS "dosage." Kilohertz-frequency SCS produces analgesia without paresthesia and is thought, therefore, not to activate afferent axons. We show that paresthesia is absent not because axons do not spike but because they spike asynchronously. In a pain patient, selectively increasing SCS frequency abolished paresthesia and epidurally recorded evoked compound action potentials (ECAPs). Dependence of ECAP amplitude on SCS frequency was reproduced in pigs, rats, and computer simulations and is explained by overdrive desynchronization: spikes desychronize when axons are stimulated faster than their refractory period. Unlike synchronous spikes, asynchronous spikes fail to produce paresthesia because their transmission to somatosensory cortex is blocked by feedforward inhibition. Our results demonstrate how stimulation frequency impacts synchrony based on axon properties and how synchrony impacts sensation based on circuit properties. Competing Interests: Declaration of interests S.A.P. has received grant funding from Boston Scientific. S.A.P. has received compensation from Boston Scientific and Presidio Medical as a member of their scientific advisory boards. T.Z. and R.E. are paid employees of Boston Scientific and own stock in Boston Scientific. T.Z. has received royalty payments from Boston Scientific for licensed IP. R.E. owns stock in NeuroPace. N.Y. is now a paid employee of Annexon Biosciences. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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