The rostral ventromedial medulla (RVM) exerts both inhibitory and excitatory controls over nociceptive neurons in the spinal cord and medullary dorsal horn. Selective ablation of
mu-opioid receptor (MOR)-expressing neurons in the RVM using
saporin conjugated to the MOR agonist
dermorphin-saporin (derm-sap) attenuates stress and injury-induced behavioral
hypersensitivity, yet the effect of RVM derm-sap on the functional integrity of the descending inhibitory system and the properties of RVM neurons remain unknown. Three classes of RVM neurons (on-cells, off-cells, and neutral cells) have been described with distinct responses to noxious stimuli and MOR agonists. Using single unit recording in lightly anesthetized rats, RVM neurons were characterized after microinjections of derm-sap or
saporin. Derm-sap treatment resulted in a reduction in on-cells and off-cells when compared to
saporin controls (P < 0.05). The number of neutral cells remained unchanged. After derm-sap treatment, RVM microinjections of the
glutamate receptor agonist
homocysteic acid increased tail-flick latencies, whereas the MOR agonist
DAMGO had no effect. Furthermore, electrical stimulation of the periaqueductal gray produced
analgesia in both derm-sap and
saporin controls with similar thresholds. Microinjection of
kynurenic acid, a
glutamate receptor antagonist, into the RVM disrupted periaqueductal gray stimulation-produced
analgesia in both
saporin-treated and derm-sap-treated rats. These results indicate that MOR-expressing neurons in the RVM are not required for
analgesia produced by either direct or indirect activation of neurons in the RVM.