Opioids modulate N-methyl- d-aspartic acid (NMDA)-evoked responses of neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis)

Abstract

Extracellular single unit recordings were made from 74 neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis). N-methyl- d-aspartic acid (NMDA) excited nociceptive as well as non-nociceptive neurons. NMDA receptor antagonist, dl-2-Amino-5-Phosphonovaleric acid (AP-5), blocked the NMDA-evoked excitation. Microiontophoretic application of a selective μ-opioid receptor agonist, [ d-Ala 2,N-Me-Phe 4,Gly 5-ol]lenkephalin (DAMGO), reduced the NMDA-evoked responses of 100% of nociceptive specific (NS), 93% of wide dynamic range (WDR) and 86% of low threshold (LT) neurons in the superficial and deeper dorsal horn of the medulla. In contrast, application of a selective δ 1-opioid receptor agonist, [ d-Pen 2,5]enkephalin (DPDPE), reduced the NMDA-evoked responses of 90% of NS neurons, 72% of WDR neurons and 67% of LT neurons in the superficial and deeper dorsal horn of the medulla. DPDPE also produced excitatory or biphasic effects. The inhibitory actions of DAMGO and DPDPE were reversed by naloxone and/or 7-benzylidenenaltrexone (BNTX), μ- and δ 1-receptor antagonists. It is concluded that μ- and σ-opioid receptor agonists produce a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive and non-nociceptive neurons in the medullary dorsal horn.