Medullary circuits for nociceptive modulation

Neurons in the medullary raphe are critical to opioid analgesia through descending projections to the dorsal horn. Work in anesthetized rats led to the postulate that nociceptive suppression results from tonic activation of nociceptive-inhibiting neurons and tonic inhibition of nociceptive-facilitating neurons. However, morphine does not cause tonic changes in raphe neuronal firing in unanesthetized rodents. Recent work suggests that a drop in activity of nociceptive-inhibiting neurons synchronizes nociceptive circuits and a burst of activity in nociceptive-facilitating neurons facilitates withdrawal magnitude. After morphine, the phasic responses of raphe cells are suppressed along with nociceptive withdrawals. The results suggest a new model of brainstem modulation of nociception in which the medullary raphe facilitates nociceptive reactions when noxious input occurs and may modulate other functions between injurious events.

► Opioid analgesia depends on descending modulation from the medullary raphe. ► Opioids produce analgesia without altering the tonic discharge of medullary neurons. ► Normally, phasic neuronal responses of brainstem cells facilitate nociception. ► Morphine produces analgesia by blocking the phasic responses of brainstem cells. ► Brainstem cells may modulate non-nociceptive functions during pain-free periods.