Biphasic Modulation of Spinal Visceral Nociceptive Transmission From the Rostroventral Medial Medulla in the Rat

Abstract

Descending inhibitory and facilitatory influences from the rostroventral medulla (RVM) on responses of lumbosacral spinal neurons to noxious colorectal distension (CRD, 80 mmHg, 20 s) were studied. At 25 sites in the RVM, electrical stimulation produced biphasic effects, facilitating responses of spinal neurons to CRD at lesser intensities of stimulation (5-25 microA) and inhibiting responses of the same neurons at greater intensities of stimulation (50-100 microA). At 38 other sites in the RVM, electrical stimulation produced only intensity-dependent inhibition of neuron responses to CRD. At another 13 sites in the RVM, electrical stimulation (5-100 microA) produced only facilitatory effects on responses to CRD. Descending modulatory effects were selective for distension-evoked activity; spontaneous activities of the same spinal neurons were not significantly affected by electrical stimulation that either facilitated or inhibited neuron responses to CRD. Neuron responses to graded CRD (20-100 mmHg) were positively accelerating functions that were shifted leftward or rightward, respectively, by lesser, facilitatory intensities or greater, inhibitory intensities of RVM stimulation. L-glutamate microinjection into the RVM replicated the effects of electrical stimulation, producing similar biphasic modulatory effects as produced by electrical stimulation. Microinjection of glutamate into the RVM at a low dose (5 nmoles) facilitated responses of spinal neurons to CRD and inhibited responses of the same neurons at a greater dose (50 nmoles). In some experiments, microinjection of lidocaine (0.5 microl of 4% solution) or the neurotoxin ibotenic acid (0.5 microl, 10 microg) into the RVM produced reversible or long-lasting, respectively, decreases in spontaneous activity and responses of spinal neurons to CRD. These results reveal that spinal visceral nociceptive transmission is subject to a tonic descending excitatory influence from the RVM and that descending modulatory effects from the RVM on visceral nociceptive transmission are qualitatively similar to modulation of cutaneous nociceptive transmission.