Raphe magnus serotonergic neurons tonically modulate nociceptive transmission

Serotonin-containing neurons in the medullary raphe magnus (RM) have long been thought to be important mediators of descending nociceptive inhibition. Although pharmacologic and behavioral studies support this idea, recent physiologic evidence demonstrates that RM serotonergic cells do not respond to antinociceptive stimulation in the periaqueductal gray or analgesic doses of morphine with a change in discharge rate. Instead, serotonergic cell discharge is likely to influence the outcome of modulatory circuits by tonically modulating the effects of other synaptic connections in the dorsal horn. Because serotonergic cells discharge in relation to sleep and wake cycles, RM serotonergic cells are hypothesized to subserve the relative decrease in nociceptive responsiveness observed during waking compared to slow-wave sleep.