PT  - JOURNAL ARTICLE
AU  - Thomas F. Finnegan
AU  - De-Pei Li
AU  - Shao-Rui Chen
AU  - Hui-Lin Pan
TI  - Activation of μ-Opioid Receptors Inhibits Synaptic Inputs to Spinally Projecting Rostral Ventromedial Medulla Neurons
AID  - 10.1124/jpet.103.064808
DP  - 2004 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 476--483
VI  - 309
IP  - 2
4099  - http://jpet.aspetjournals.org/content/309/2/476.short
4100  - http://jpet.aspetjournals.org/content/309/2/476.full
SO  - J Pharmacol Exp Ther2004 May 01; 309
AB  - The rostral ventromedial medulla (RVM) is a major locus for the descending control of nociception and opioid analgesia. However, it is not clear how opioids affect synaptic inputs to RVM neurons. In this study, we determined the effect of μ-opioid receptor activation on excitatory and inhibitory synaptic transmission in spinally projecting RVM neurons. RVM neurons were retrogradely labeled with a fluorescent tracer injected into the dorsal horn of the spinal cord in rats. Whole-cell voltage-clamp recordings were performed on labeled RVM neurons in brain slices in vitro. The μ-receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 1 μM) significantly decreased the amplitude of evoked excitatory postsynaptic currents (EPSCs) in 52% (9 of 17) of labeled cells. DAMGO also significantly reduced the amplitude of evoked inhibitory postsynaptic currents (IPSCs) in 69% (11 of 16) of cells examined. Furthermore, DAMGO significantly decreased the frequency of miniature EPSCs in 55% (15 of 27) of cells and significantly decreased the frequency of miniature IPSCs in all 12 cells studied. Although most EPSCs and IPSCs were mediated by glutamate and GABA, the nicotinic and glycine receptor antagonists attenuated EPSCs and IPSCs, respectively, in some labeled RVM neurons. Immunocytochemical labeling revealed that only 35% of recorded RVM neurons were tryptophan hydroxylase-positive, and 15% cells had GABA immunoreactivity. Thus, this study provides important functional evidence that activation of μ-opioid receptors decreases the release of both excitatory and inhibitory neurotransmitters onto most spinally projecting RVM neurons. The American Society for Pharmacology and Experimental Therapeutics