Involvement of opioid receptors in the CGRP8-37-induced inhibition of the activity of wide-dynamic-range neurons in the spinal dorsal horn of rats

J Neurosci Res. 2004 Jul 1;77(1):148-52. doi: 10.1002/jnr.20111.

Abstract

The present study was performed to explore the involvement of opioid receptors in the calcitonin gene-related peptide 8-37 (CGRP8-37, an antagonist of CGRP receptor)-induced inhibition of the activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of rats. Extracellular recording was performed with a multibarrelled glass micropipette, and the chemicals were delivered by micro-iontophoresis. The discharge frequency of WDR neurons was evoked by subcutaneous electrical stimulation applied to the ipsilateral hindpaw. Iontophoretic application of CGRP8-37 by an ejection current of 160 nA induced significant inhibition of the discharge frequency of WDR neurons. The inhibitory effect of CGRP8-37 on the activity of WDR neurons was attenuated by later iontophoretic application of the opioid antagonist naloxone. Furthermore, the effect of CGRP8-37 was attenuated by either iontophoretic application of the kappa-receptor antagonist nor-binaltorphimine (nor-BNI) or the mu-receptor antagonist beta-funaltrexamine (beta-FNA) but not by the delta-receptor antagonist naltrindole. The results indicate that kappa- and mu-opioid receptors on the membrane of WDR neurons are involved in the modulation of CGRP8-37-induced antinociception in dorsal horn of the spinal cord in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism
  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Electric Stimulation
  • Male
  • Narcotic Antagonists / pharmacology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Pain / drug therapy
  • Pain / metabolism*
  • Pain / physiopathology
  • Peptide Fragments / pharmacology*
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / metabolism

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Narcotic Antagonists
  • Peptide Fragments
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • calcitonin gene-related peptide (8-37)
  • Calcitonin Gene-Related Peptide