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Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

Publication ,  Journal Article
Zhang, TC; Janik, JJ; Peters, RV; Chen, G; Ji, R-R; Grill, WM
Published in: J Neurophysiol
July 2015

Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry.

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Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

July 2015

Volume

114

Issue

1

Start / End Page

284 / 300

Location

United States

Related Subject Headings

  • Spinal Cord Stimulation
  • Spinal Cord
  • Sensory Receptor Cells
  • Sciatic Nerve
  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Peripheral Nervous System Diseases
  • Neurology & Neurosurgery
  • Neuralgia
  • Neural Inhibition
 

Citation

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Zhang, T. C., Janik, J. J., Peters, R. V., Chen, G., Ji, R.-R., & Grill, W. M. (2015). Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control. J Neurophysiol, 114(1), 284–300. https://doi.org/10.1152/jn.00147.2015
Zhang, Tianhe C., John J. Janik, Ryan V. Peters, Gang Chen, Ru-Rong Ji, and Warren M. Grill. “Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.J Neurophysiol 114, no. 1 (July 2015): 284–300. https://doi.org/10.1152/jn.00147.2015.
Zhang TC, Janik JJ, Peters RV, Chen G, Ji R-R, Grill WM. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control. J Neurophysiol. 2015 Jul;114(1):284–300.
Zhang, Tianhe C., et al. “Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.J Neurophysiol, vol. 114, no. 1, July 2015, pp. 284–300. Pubmed, doi:10.1152/jn.00147.2015.
Zhang TC, Janik JJ, Peters RV, Chen G, Ji R-R, Grill WM. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control. J Neurophysiol. 2015 Jul;114(1):284–300.

Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

July 2015

Volume

114

Issue

1

Start / End Page

284 / 300

Location

United States

Related Subject Headings

  • Spinal Cord Stimulation
  • Spinal Cord
  • Sensory Receptor Cells
  • Sciatic Nerve
  • Receptors, GABA-A
  • Rats, Sprague-Dawley
  • Peripheral Nervous System Diseases
  • Neurology & Neurosurgery
  • Neuralgia
  • Neural Inhibition