Neurons of the rostral ventromedial medulla (RVM) have been implicated in the modulation of nociceptive transmission. In order to further analyze their role in pain behavior, we studied their activity while eliciting the tail flick reflex with noxious heat. Recording sites were regions in the RVM from which microstimulation (less than or equal to 10 microA, 400 mu sec, 50 Hz continuous pulse trains) inhibited the tail flick reflex. Extracellular unit activity and tail temperature were recorded, stored, and plotted with reference to either the time of tail flick or the time when the stimulating temperature reached 45 degrees C. Neuronal discharges were found to be either increased (on-cells), decreased (off-cells), or unchanged around the time of the tail flick. The decreases in discharge were more closely correlated with the tail flick behavior than with the temperature of the stimulus. These off-cells were located at sites of lowest threshold for tail flick inhibition and tended to be ventral to on-cells. We propose that off-cells must pause if the tail flick is to occur, and that this pausing allows the transmission of nociceptive input through spinal reflex loops.
Analgesia results when opiates are microinjected into the rostral ventromedial medulla (RVM). This region, which includes the nucleus raphe magnus and the adjacent reticular formation, is rich in immunoreactive enkephalin-containing neurones and terminals, and contains neurones that project to the spinal cord dorsal horn where they inhibit identified nociceptive spinothalamic tract neurones. Although opiates have previously been reported either to excite or inhibit RVM cells, the possibility of an opiate effect being consistent within a physiologically defined subclass has not been examined. Recently we described a class of neurone in the RVM (the off-cell) that abruptly pauses just before a heat-evoked tail-flick reflex. If off-cells are made to fire continuously by direct electrical stimulation of the RVM, the tail-flick reflex does not occur. We report here that analgesic doses of morphine completely eliminate the pause in firing that precedes the tail-flick reflex. We propose that this disinhibition of off-cells in the RVM is a primary process contributing to opiate inhibition of nociceptor-induced reflexes.
This report describes how the threshold for extracellular, electrical stimulation of cell bodies in the rat's rostromedial medulla depends on the distance to the stimulating electrode. A monopolar microelectrode both delivered current pulses near medullospinal neurons and, after decay of the stimulus artifact, detected whether an orthodromic spike had occurred by collision of that spike with a suitably timed antidromic spike initiated at the thoracic spinal cord. The liminal current and the height of antidromic spikes were noted at a series of vertical electrode positions. Regression analysis was performed to determine whether threshold and the inverse of peak-to-peak spike height varied more as the radial distance or its square. The square relationship provided a much better fit for threshold and a marginally better fit for the inverse of spike height. The spatial decline in excitability (K2) averaged 859 microA/mm2, falling within the range of values found for fibers and cell bodies in other studies. The constant of spatial decline in spike height (C2) in millivolts per square millimeter was positively correlated with K2. Both C2 and K2 were negatively correlated with conduction velocity. From threshold distance curves fitted by regression analysis, the mean separation of sites of spike maxima and threshold minima along each electrode path was 16 micron; the estimated distance from these sites to, respectively, the loci of spike generation and spike excitation were positively correlated and similar. The variation of C2 and K2 with conduction velocity may be due either to an influence of the size and shape of the dendritic tree on the spatial decrement of excitability and spike height or to a confounding in the studied equations of the space-independent effect of the size of a cell body on spike height and excitability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.