OPIOIDS MODULATE N-METHYL-D-ASPARTIC ACID (NMDA)-EVOKED RESPONSES OF TRIGEMINOTHALAMIC NEURONS

1. The present study investigated opioid-mediated modulation of N-meth yl-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. Microiontopho retic application of NMDA activated 18/19 trigeminothalamic neurons. A dministration of [D-Ala(2), N-MePhe(4),Gly(5)-ol]-Enkephalin, a select ive mu-opioid receptor agonist, reduced the NMDA-evoked responses in 7 7% of trigeminothalamic neurons. [D-Pen(2,5)]-Enkephalin, a selective delta-opioid receptor agonist, produced inhibition of NMDA-evoked resp onses in 36% of neurons.3. We suggest that 1) NMDA-receptor activation excites trigeminothalamic nociceptive neurons and may, therefore, med iate nociceptive transmission in the medullary dorsal horn; and 2) the predominantly inhibitory modulation of NMDA-receptor-mediated respons es of nociceptive trigeminothalamic neurons by activation of mu- and d elta-opioid receptors may provide a neural mechanism for the antinocic eptive actions of opioids.