μ-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat

Timothy J. Grudt, John T. Williams

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

The actions of opioid agonists in the substantia gelatinosa are important for their antinociceptive effects. In order to identify possible mechanisms underlying opioid actions in the substantia gelatinosa, the pre- and postsynaptic effects of opioid agonists on neurons of the substantia gelatinosa were examined using a brain slice preparation. Intracellular recordings were made from neurons of the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis in guinea pig and rat. To correlate morphology and electrophysiology, neurons were filled with biocytin and visualized using HRP. The majority of neurons (86%) were hyperpolarized by [Met]5enkephalin (ME), and this was mimicked by the μ-opioid agonist (D- Ala2,N-Me-Phe4,Gly5-ol)enkephalin (DAMGO) but not the δ-opioid agonist (D-Pen2,5)enkephalin (DPDPE). Naloxone (300 nM) shifted the DAMGO dose- response 213-fold to the right, giving an estimated K(D) of 1.4 nM. Under voltage clamp, the ME current reversed polarity at the potassium equilibrium potential, indicating the hyperpolarization was due to an increase in potassium conductance. EPSPs mediated by glutamate were evoked by stimulating the spinal trigeminal tract, which contains the primary afferent fibers that synapse in the spinal trigeminal nucleus. The excitation produced by stimulating the spinal trigeminal tract was greatly enhanced in the presence of glycine and GABA(A) receptor antagonists, indicating that local inhibitory circuitry is activated by exciting the primary afferents. The EPSPs were reduced by μ- but not δ-opioid receptor activation. The degree of inhibition varied from 0 to 100%. These results indicate that opioid agonists cause inhibition in the substantia gelatinosa by both pre- and postsynaptic actions.

Original languageEnglish (US)
Pages (from-to)1646-1654
Number of pages9
JournalJournal of Neuroscience
Volume14
Issue number3 II
StatePublished - Mar 1 1994

Keywords

  • DAMGO
  • GABA
  • glycine
  • morphology
  • naloxone
  • presynaptic inhibition
  • substantia gelatinosa
  • μ-opioid

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'μ-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat'. Together they form a unique fingerprint.

  • Cite this