Opioids modulate N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons.
1. The present study investigated opioid-mediated modulation of N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in rats anesthetized with urethane. 2. Microiontophoretic application of NMDA activated 18/19 trigeminothalamic neurons. Administration of [D-Ala2, N-Me-Phe4,Gly5-ol]-Enkephalin, a selective mu-opioid receptor agonist, reduced the NMDA-evoked responses in 77% of trigeminothalamic neurons. [D-Pen2,5]-Enkephalin, a selective delta-opioid receptor agonist, produced inhibition of NMDA-evoked responses in 36% of neurons. 3. We suggest that 1) NMDA-receptor activation excites trigeminothalamic nociceptive neurons and may, therefore, mediate nociceptive transmission in the medullary dorsal horn; and 2) the predominantly inhibitory modulation of NMDA-receptor-mediated responses of nociceptive trigeminothalamic neurons by activation of mu- and delta-opioid receptors may provide a neural mechanism for the antinociceptive actions of opioids.
Department of Physiology, Meharry Medical College, Nashville, Tennessee 37208, USA.
X M
XM
Wang
S S
SS
Mokha
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013788:Thalamus / Q000166:cytology / Q000187:drug effects*; D014278:Trigeminal Nuclei / Q000166:cytology / Q000187:drug effects*
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016202:N-Methylaspartate; D020881:Enkephalin, D-Penicillamine (2,5)-