Descending modulation of pain

Abstract

Brainstem structures engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain. The final output for this bidirectional control is the rostral ventromedial medulla (RVM), which shapes sensory processing via relays between the spinal cord and brain, ultimately influencing pain perception via On and Off cells. In this chapter we look at how the balance between these cells' output can be reversibly and transiently altered so that nociceptive signals are enhanced or suppressed. Moreover, we look at how the descending modulatory system may become maladaptive and durably altered so that pain outlasts its biological usefulness and cause; following nerve injury for example, increased descending facilitatory output may establish an unrelenting feed-forward compensatory circuit between the periphery, spinal cord and brain to support chronic pain. We discuss how descending serotonergic action at spinal receptors is a major player in this top-down pain mechanism, and also look at the contribution of the descending noradrenergic system. Finally, we suggest that activity in the spino-bulbo-spinal circuit influences analgesic drug efficacy, and speculate on the contribution of aberrant supraspinal function to centrally-based pains such as fibromyalgia syndrome (FMS), as well as opioid-induced hyperalgesia.