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

Publication ,  Journal Article
Gilbert, JE; Titus, N; Zhang, T; Esteller, R; Grill, WM
Published in: eNeuro
September 2022

Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds-minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal administration of bicuculline shifted neural responses to low-amplitude stimulation in both the model and experiment, suggesting that analgesia is dependent on segmental GABAergic mechanisms. Our results support the hypothesis that low-frequency subperception SCS generates rapid analgesia by activating a small number of DC axons which inhibit DH neuron activity via surround inhibition.

Duke Scholars

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Published In

eNeuro

DOI

EISSN

2373-2822

ISSN

2373-2822

Publication Date

September 2022

Volume

9

Issue

5

Start / End Page

ENEURO.0058 / ENEU22.2022

Related Subject Headings

  • Urethane
  • Spinal Cord Stimulation
  • Spinal Cord
  • Rats
  • Posterior Horn Cells
  • Neuralgia
  • Bicuculline
  • Animals
  • 1109 Neurosciences
 

Citation

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Gilbert, J. E., Titus, N., Zhang, T., Esteller, R., & Grill, W. M. (2022). Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement. ENeuro, 9(5), ENEURO.0058-ENEU22.2022. https://doi.org/10.1523/eneuro.0058-22.2022
Gilbert, John E., Nathan Titus, Tianhe Zhang, Rosana Esteller, and Warren M. Grill. “Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement.ENeuro 9, no. 5 (September 2022): ENEURO.0058-ENEU22.2022. https://doi.org/10.1523/eneuro.0058-22.2022.
Gilbert JE, Titus N, Zhang T, Esteller R, Grill WM. Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement. eNeuro. 2022 Sep;9(5):ENEURO.0058-ENEU22.2022.
Gilbert, John E., et al. “Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement.ENeuro, vol. 9, no. 5, Sept. 2022, p. ENEURO.0058-ENEU22.2022. Epmc, doi:10.1523/eneuro.0058-22.2022.
Gilbert JE, Titus N, Zhang T, Esteller R, Grill WM. Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement. eNeuro. 2022 Sep;9(5):ENEURO.0058-ENEU22.2022.

Published In

eNeuro

DOI

EISSN

2373-2822

ISSN

2373-2822

Publication Date

September 2022

Volume

9

Issue

5

Start / End Page

ENEURO.0058 / ENEU22.2022

Related Subject Headings

  • Urethane
  • Spinal Cord Stimulation
  • Spinal Cord
  • Rats
  • Posterior Horn Cells
  • Neuralgia
  • Bicuculline
  • Animals
  • 1109 Neurosciences