Activation of brainstem N‐methyl‐D‐aspartate receptors is required for the analgesic actions of morphine given systemically. (Oregon Health Sciences University, Portland, OR) Pain. 2001;92:129–138.

Abstract

This study was designed to characterize the contribution of N‐methyl‐D‐aspartate (NMDA) and non‐NMDA‐mediated excitatory transmission within the rostral ventromedial medulla (RVM) to activation of brainstem inhibitory output neurons and analgesia produced by systemic morphine administration. The results highlight 2 important aspects of RVM pain modulatory circuits. First, morphine given systemically produces it analgesic effect at least in part by recruiting an NMDA‐mediated excitatory process to activate off‐cells within the RVM. This excitatory process plays a role in the analgesic synergy produced by simultaneous μ‐opioid activation at different levels of the neuraxis. Second, reflex‐related activation of on‐cells is medicated by a non‐NMDA receptor, and this activation does not appear to play a significant role in regulating reflex responses to acute noxious stimuli. Excitatory amino acid‐mediated excitation, thus, has 2 distinct roles within the RVM, activating off‐cells and on‐cells under different conditions.