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Journal of Neuroscience, Vol 14, 1646-1654, Copyright © 1994 by Society for Neuroscience
mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat
TJ Grudt and JT Williams
Vollum Institute, Oregon Health Sciences University, Portland 97201.
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 mu-opioid agonist
(D-Ala2,N-Me-Phe4,Gly5- ol)enkephalin (DAMGO) but not the delta-opioid
agonist (D- Pen2,5)enkephalin (DPDPE). Naloxone (300 nM) shifted the DAMGO
dose- response 213-fold to the right, giving an estimated KD 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 GABAA receptor antagonists,
indicating that local inhibitory circuitry is activated by exciting the
primary afferents. The EPSPs were reduced by mu- but not delta-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.
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