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.

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.

Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI.