Research Article

Involvement of ryanodine receptors in tetanic sciatic stimulation-induced long-term potentiation of spinal dorsal horn and persistent pain in rats

  1. Ning Lü1,*,
  2. Long-Zhen Cheng1,
  3. Yu-Qiu Zhang1,
  4. Bai-Chang Lü2,
  5. Yun-Qing Li2,
  6. Zhi-Qi Zhao1,*

Article first published online: 8 FEB 2012

DOI: 10.1002/jnr.22799

Issue

Journal of Neuroscience Research

Journal of Neuroscience Research

Volume 90, Issue 5, pages 1096–1104, May 2012

Additional Information

How to Cite

Lü, N., Cheng, L.-Z., Zhang, Y.-Q., Lü, B.-C., Li, Y.-Q. and Zhao, Z.-Q. (2012), Involvement of ryanodine receptors in tetanic sciatic stimulation-induced long-term potentiation of spinal dorsal horn and persistent pain in rats. J. Neurosci. Res., 90: 1096–1104. doi: 10.1002/jnr.22799

Author Information

  1. 1

    Institute of Neurobiology, Institutes of Brain Science and State Key laboratory of Medical Neurobiology, Fudan University, Shanghai, China

  2. 2

    Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, China

*PhD, Institute of Neurobiology, Fudan University, Shanghai, 200032, China

Publication History

  1. Issue published online: 7 MAR 2012
  2. Article first published online: 8 FEB 2012
  3. Manuscript Accepted: 22 AUG 2011
  4. Manuscript Revised: 19 AUG 2011
  5. Manuscript Received: 30 MAY 2011

Funded by

  • National Natural Science Fund of China. Grant Numbers: 30600178, 30830044
  • National Basic Research Program of China. Grant Numbers: 2007CB512303, 2007CB512502

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Keywords:

  • ryanodine receptor;
  • long-term potentiation;
  • persistent pain;
  • nociceptive neruons;
  • spinal cord

Abstract

Tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn and persistent pain, suggesting that spinal LTP may be a substrate for central sensitization of the pain pathway. However, its cellular mechanism remains unclear. The present study provides electrophysiological and behavioral evidence for the involvement of ryanodine receptor (RyR) in the induction of spinal LTP and persistent pain in rats. The specific inhibitor of ryanodine receptor, ryanodine and dantrolene, dose dependently blocked the induction, but not maintenance, of spinal LTP and reduced persistent pain behaviors induced by tetanic sciatic stimulation. Both cyclic ADP ribose (cADPR), an endogenous agonist of RyR, and (±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644), an agonist of L-type calcium channel, attenuated ryanodine-induced inhibition. Immunohistochemistry and electron microscopic observation showed that RyR subtypes RyR1 and RyR3 were located in the spinal dorsal horn. The results suggest that RyRs are involved in synaptic plasticity of the spinal pain pathway and may be a novel target for treating pain. © 2012 Wiley Periodicals, Inc.

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