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

M. M. Heinricher, S. McGaraughty

    Research output: Contribution to journalArticlepeer-review

    55 Scopus citations

    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 firing 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.

    Original languageEnglish (US)
    Pages (from-to)247-255
    Number of pages9
    JournalPain
    Volume75
    Issue number2-3
    DOIs
    StatePublished - Jan 1998

    Keywords

    • Descending control
    • Kynurenate
    • Microinjection
    • Nucleus raphe magnus
    • Opioid analgesia
    • Pain modulation

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine

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