Discharge of Raphe Magnus on and offCells Is Predictive of the Motor Facilitation Evoked by Repeated Laser Stimulation

Abstract

Medullary raphe magnus (RM) ON and OFF cells are thought to modulate spinal nociception by gating withdrawals evoked by noxious stimulation. To test whether withdrawal initiation is the target of RM modulation, we examined the relationship between ON and OFF cell discharge and motor withdrawal evoked by noxious laser heat in halothane-anesthetized rats. The cellular responses of both cell types began during the 50 msec after onset of the tail flick, peaked within 200 msec, and outlasted the duration of the motor reaction. Thus, it is unlikely that the target of ON and OFF cell modulation is withdrawal initiation; instead, ON and OFF cells may modulate reactions to repeated noxious stimulation. We therefore tested whether laser heat-evoked changes in RM cell discharge were predictive of the modulatory effects of one noxious stimulus on the reaction to a subsequent noxious stimulus. Two pulses of laser heat were presented at interpulse intervals of 0.8, 2.0, or 10.0 sec. The motor withdrawal evoked by the second pulse was significantly enhanced relative to that evoked by the first pulse. The observed motor enhancement depended on supraspinal input because it was not present in spinalized rats. Comparison of the relative changes in motor and cellular activity preceding double laser heat stimulation revealed parallel changes between motor facilitation, decreases in OFF cell discharge, and increases in ON cell discharge. This finding suggests a preparatory role for RM ON and OFF cells in enhancing reactions to a noxious stimulus that closely follows another noxious stimulus.

The spinal cord, anesthesia and immobility: A re-examination

“…The RVM receives input from the PAG. More recent data suggest that ON and OFF cells, in addition to being involved in initiation of movement, might modulate movement after it has begun or in response to repeated stimuli [19]. GABA antagonists decrease ON cell activity, while increasing OFF cell spontaneous activity, similar to what we reported for ISO [20].…”

“…Furthermore, it is unclear to what extent anesthetic action in the spinal cord affects evoked activity of ON and OFF cells. Because ON and OFF cells are likely involved in the initiation of movement as well as its continuation [19], there is likely to be a complex interplay among sensorimotor processing in the spinal cord, ON and OFF cells and anesthetic actions in spinal cord and the RVM. A potential role for ON cells in initiating/maintaining locomotor activity in the spinal cord is discussed in a companion paper in these proceedings (Jinks).…”

Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions

“…(S)-3,4-DCPG also reduced tail flick-induced ON cell burst and OFF cell pause and increased the onset of both ON cell burst and OFF cell pause in the same animals. A delayed onset of the ON cell burst, as well as the reduction of the burst of firing, proved to be critical events in the occurrence of antinociception (Foo and Mason 2003;Heinricher et al 1989;Jinks et al 2004). Moreover, an inhibition of pain transmission correlates with an increase of spontaneous OFF cell activity and a reduction of its pause as well as a delay of the pause onset (Heinricher and Tortorici 1994).…”

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

“…Conversely, on-cells exert a net facilitatory effect on nociception. Periods of ongoing on-cell discharge are associated with enhanced nociception (Heinricher et al, 1989;Ramírez and Vanegas, 1989;Bederson et al, 1990;Foo and Mason, 2003); similarly, direct selective activation of on-cells produces hyperalgesia in lightly anesthetized rats (Neubert et al, 2004). The role of neutral cells remains to be elucidated (Potrebic et al, 1994;Mason, 1997).…”