Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

Mol Pain. 2010 Jan 20;6:1. doi: 10.1186/1744-8069-6-1.


Background: Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.

Results: By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP(3)R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca(2+)]i in small DRG neurons.

Conclusions: These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism
  • Animals
  • Caffeine / pharmacology
  • Cells, Cultured
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Immunohistochemistry
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism
  • Nitric Oxide / metabolism
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Organ Culture Techniques
  • Pain / metabolism*
  • Pain / physiopathology
  • Patch-Clamp Techniques
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Ryanodine Receptor Calcium Release Channel
  • Nitric Oxide
  • Caffeine