The role of excitatory amino acid transmission within the rostral ventromedial medulla in the antinociceptive actions of systemically administered morphine

Two classes of neurons with distinct responses to opioids have been identif ied in the rostral ventromedial medulla (RVM), a region with a well-documen ted role in nociceptive modulation 'Off-cells' are activated, indirectly, b y opioids, and are likely to exert a net inhibitory effect on nociceptive p rocessing. 'On-cells' are directly inhibited by opioids, and there is evide nce that these neurons can, under various conditions, facilitate nociceptio n. We showed previously that excitatory amino acid (EAA) neurotransmission is crucial to the nocifensor reflex-related on-cell burst, but plays little role in maintaining the ongoing activity of off-cells. The aim of the pres ent study was to determine whether EAA transmission contributes to the acti vation of off-cells and the concomitant behavioral antinociception that fol low systemic opioid administration. The non-selective EAA receptor antagoni st kynurenate was infused into the RVM (1 nmol/200 nl) of lightly anestheti zed rats prior to administration of morphine (1.5 mg/kg i.v). Off-cell, on- cell and neutral cell firing, as well as, tail flick response (TF) latencie s were recorded. Kynurenate, significantly attenuated the characteristic op ioid activation of off-cells. As a group, off-cells in kynurenate-treated a nimals did not become continuously active, and continued to exhibit tail-fl ick related pauses in firing. On-cell and neutral cell responses to opioid administration were unchanged. Opioid inhibition of the TF was also reduced , although baseline TF latency was unaffected, by RVM kynurenate. EAA-media ted activation of off-cells, thus has an important role in opioid analgesia . The present observations underscore the importance of excitatory interact ions among opioid-sensitive nociceptive modulatory circuits for systemic mo rphine analgesia, suggesting that such interactions are a critical factor i n the synergistic relationships which have been demonstrated among these si tes. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.