Serotonergic Modulation of Spinal Sensory Circuits

The role of serotonin (5-HT) as a mediator of the endogenous pain control system has been investigated over the last 30 years. Here we review a subset of studies that used electrophysiological techniques to study the mechanisms of action as well as the receptors mediating the spinal effects of serotonin. The works herein discussed employed in vivo or in vitro preparations of control or hyperalgesic animals. According to these reports, 5-HT triggers depressant effects on synaptic transmission limiting the release of neurotransmitters from afferent terminals or the responsiveness of NMDA receptors located in dorsal horn neurones. These mechanisms are most likely mediated by 5-HT1 receptors. In contrast, 5-HT2 receptors seem to mediate excitatory effects such as depolarisation, increased excitability, and neurotransmitter release. The role of 5-HT3 receptors is less clear as they could mediate excitatory or inhibitory effects, depending on variables such as concentration of 5-HT or the state (sensitised/unsensitised) of the spinal cord. The consequences of these spinal effects of serotonin are discussed in the context of pain and analgesia.