Serotonin (5-HT) and pain: A reappraisal of its role in the light of receptor multiplicity

Centrifugal serotonergic pathways running from the rostroventral medulla (RVM) to the dorsal horn of the spinal cord have long been considered an integral component of mechanisms of ‘descending inhibition’ limiting the access of nociceptive information to higher centres. However, the hypothesis of a generalized antinociceptive role of these serotonergic projections no longer seems tenable. Indeed, multiple serotonin (5-HT) receptor types in the dorsal horn appear to fulfil differential roles in the control of nociception, reflecting their contrasting patterns of coupling to intracellular transduction mechanisms. Further, the importance of actions of 5-HT outside the dorsal horn should not be neglected. These aspects have been synthesized into a global view of the role of 5-HT in the control of nociception.