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Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition.

Publication ,  Journal Article
Zhang, TC; Janik, JJ; Grill, WM
Published in: Journal of neurophysiology
August 2014

Spinal cord stimulation (SCS) is a clinical therapy for chronic, neuropathic pain, but an incomplete understanding of the mechanisms underlying SCS contributes to the lack of improvement in SCS efficacy over time. To study the mechanisms underlying SCS, we constructed a biophysically based network model of the dorsal horn circuit consisting of interconnected dorsal horn interneurons and a wide-dynamic range (WDR) projection neuron and representations of both local and surround receptive field inhibition. We validated the network model by reproducing cellular and network responses relevant to pain processing including wind-up, A fiber-mediated inhibition, and surround receptive field inhibition. We then simulated the effects of SCS on the activity of the WDR projection neuron and found that the response of the model WDR neuron to SCS depends on the SCS frequency; SCS frequencies of 30-100 Hz maximally inhibited the model WDR neuron, while frequencies under 30 Hz and over 100 Hz excited the model WDR neuron. We also studied the impacts on the effects of SCS of loss of inhibition due to the loss of either GABA or KCC2 function. Reducing the influence of local and surround GABAergic interneurons by weakening their inputs or their connections to the WDR neuron and shifting the anionic reversal potential of the WDR neurons upward each reduced the range of optimal SCS frequencies and changed the frequency at which SCS had a maximal effect. The results of this study provide insights into the mechanisms of SCS and pave the way for improved SCS parameter selection.

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Published In

Journal of neurophysiology

DOI

EISSN

1522-1598

ISSN

0022-3077

Publication Date

August 2014

Volume

112

Issue

3

Start / End Page

552 / 567

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Spinal Cord Stimulation
  • Rats
  • Posterior Horn Cells
  • Pain
  • Nociception
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Models, Neurological
 

Citation

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Zhang, T. C., Janik, J. J., & Grill, W. M. (2014). Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition. Journal of Neurophysiology, 112(3), 552–567. https://doi.org/10.1152/jn.00254.2014
Zhang, Tianhe C., John J. Janik, and Warren M. Grill. “Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition.Journal of Neurophysiology 112, no. 3 (August 2014): 552–67. https://doi.org/10.1152/jn.00254.2014.
Zhang, Tianhe C., et al. “Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition.Journal of Neurophysiology, vol. 112, no. 3, Aug. 2014, pp. 552–67. Epmc, doi:10.1152/jn.00254.2014.

Published In

Journal of neurophysiology

DOI

EISSN

1522-1598

ISSN

0022-3077

Publication Date

August 2014

Volume

112

Issue

3

Start / End Page

552 / 567

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Spinal Cord Stimulation
  • Rats
  • Posterior Horn Cells
  • Pain
  • Nociception
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Models, Neurological