Nociceptin inhibits excitatory but not inhibitory transmission to substantia gelatinosa neurones of adult rat spinal cord

Neuroscience. 2002;109(2):349-58. doi: 10.1016/s0306-4522(01)00459-6.

Abstract

Although intrathecal administration of nociceptin, an endogenous ligand of the opioid receptor-like1 receptor, exhibits an antinociceptive effect in various pain models, cellular mechanisms underlying this action are still unknown. Here, we investigated the effects of nociceptin on excitatory and inhibitory synaptic transmission to substantia gelatinosa neurones of an adult rat spinal cord slice with an attached dorsal root by use of the blind whole-cell patch-clamp technique; this was done under the condition of a blockade of a hyperpolarising effect of nociceptin. In about 70% of the neurones examined, nociceptin (1 microM) reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) which were monosynaptically evoked by stimulating Adelta- or C-afferent fibres; the inhibition of C-fibre EPSCs (50+/-6%, n=11) was larger than that of Adelta-fibre EPSCs (30+/-5%, n=23; P<0.05). Each of the nociceptin actions was dose-dependent in a concentration range of 0.1 to 1 microM, and was largely suppressed by a selective opioid receptor-like1 receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (3 microM). Nociceptin (1 microM) also decreased miniature EPSCs frequency by 22+/-6% (n=7) while not affecting their amplitude. Responses of substantia gelatinosa neurones to bath-applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (10 microM) were not changed by nociceptin. Both electrically evoked and miniature inhibitory postsynaptic currents, mediated by either the GABA(A) or glycine receptor, were unaffected by nociceptin. These results indicate that nociceptin suppresses excitatory but not inhibitory synaptic transmission to substantia gelatinosa neurones through the activation of the opioid receptor-like1 receptor; this action is pre-synaptic in origin. Considering that the substantia gelatinosa is the main part of termination of Adelta- and C-fibres transmitting nociceptive information, the present finding would account for at least a part of the inhibitory action of nociceptin on pain transmission. Nociceptin could inhibit more potently slow-conducting than fast-conducting pain transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism*
  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Glutamic Acid / metabolism
  • Male
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Nociceptors / cytology
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Opioid Peptides
  • Glutamic Acid
  • nociceptin