Analysis of excitatory amino acid transmission within the rostral ventromedial medulla: implications for circuitry

Pain. 1998 Apr;75(2-3):247-55. doi: 10.1016/s0304-3959(97)00226-1.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacokinetics
  • Excitatory Amino Acids / metabolism*
  • Kynurenic Acid / pharmacokinetics
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / physiology
  • Neural Pathways / physiology
  • Neurons / physiology
  • Nociceptors / physiology
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / physiology


  • Excitatory Amino Acid Antagonists
  • Excitatory Amino Acids
  • Kynurenic Acid