Serotonergic neuromodulation of peripheral nociceptors

Nociception, the encoding and processing of noxious environmental stimuli by sensory neurons, functions to protect an organism from bodily damage. Activation of the terminal endings of certain sensory neurons, termed nociceptors, triggers a train of impulses to neurons in the spinal cord. Signals are integrated and processed in the dorsal spinal cord and then projected to the brain where they elicit the perception of pain. A number of neuromodulators that can affect nociceptors are released in the periphery during the inflammation that follows an initial injury. Serotonin (5-HT) is a one such proinflammatory mediator. This review discusses our current understanding of the neuromodulatory role of 5-HT, and specifically how this monoamine activates and sensitizes nociceptors. Potential therapeutic targets to treat pain are described.

► Review of serotonin's modulatory role in peripheral pain processing.
► Preclinical evidence of serotonin enhancement of thermal hyperalgesia.
► Serotonin may evoke hyperalgesia via the TRPV1 population of sensory neurons.
► Hyperalgesia can be attenuated with local serotonergic blocking agents.
► Future studies should examine the therapeutic potential of peripheral serotonergics.