title: Analysis of excitatory amino acid transmission within the rostral ventromedial medulla: implications for circuitry.
abstract: Two classes of neurons with distinct responses to opioids have been identified in the rostral ventromedial medulla (RVM), a region with a well-documented role in nociceptive modulation. 'On-cells' are directly inhibited by opioids, and opioids can thus gain access to the modulatory circuitry of the RVM by an action on these neurons. 'Off-cells' are likely to exert a net inhibitory effect on nociceptive processing, and are activated by opioids. Because the opioid activation of off-cells is indirect, it has been proposed that on-cells function as inhibitory interneurons, and that opioid-induced suppression of on-cell firing in turn activates off-cells via disinhibition. The aim of the present study was to test this possibility. We had previously shown that excitatory amino acid (EAA) neurotransmission is crucial to the nocifensor reflex-related on-cell burst. We therefore infused the non-selective EAA receptor antagonist kynurenate (0.5-2 nmol, 200-500 nl) into the RVM while recording activity of on-, off- and neutral cells in lightly anesthetized rats. Kynurenate infusions produced a significant decrease in on-cell firing, with suppression of the on-cell burst. Off-cells nonetheless continued to display a tail flick-related pause in firing. Tail flick latency was used as an index of nociceptive responsiveness, and was unaffected by kynurenate infusions. These results demonstrate that a burst of on-cell firing is not required in order for the off-cell to exhibit a reflex-related pause in discharge, and do not support the proposed crucial role for on-cells as inhibitory interneurons within the RVM. In addition, preferential suppression of on-cell tiring was not associated with an increase in tail flick latency. This suggests that, under the conditions of these experiments, on-cell discharge is not a potent regulator of moment-to-moment variations in nociceptive responsiveness.
authors.affiliation: Division of Neurosurgery, Oregon Health Sciences University, Portland 97201, USA. mmh@hood.transport.com
authors.forename: M M
authors.initials: MM
authors.lastname: Heinricher
authors.forename: S
authors.initials: S
authors.lastname: McGaraughty
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D018846:Excitatory Amino Acids / Q000378:metabolism*; D007736:Kynurenic Acid / Q000493:pharmacokinetics; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D007736:Kynurenic Acid