The following brief overview reflects our own opinion of where the most likely advances to treating
pain (unrelated to IBS and
migraine) may come from with respect to
ligands directly interacting with specific
5-HT receptors. It is fully appreciated, and possibly more likely, that
5-HT plays a modulatory role in the mediation of
analgesic effects of certain compounds, for example
tricyclic antidepressants and the newer, safer class of
serotonin/
noradrenaline re-uptake inhibitors, for example
duloxetine and
milnacipran. However, we find that recent pre-clinical findings highlight the potential of peripherally acting 5-HT(1) and
5-HT(2A) receptor agonists and centrally penetrating 5-HT(7) receptor agonists to reduce
chronic pain. We encourage experimentation using human tissues and healthy volunteers to improve the confidence in rationale of targeting such receptors for treatment of
pain in humans. However for this to happen the available pharmacological toolbox will also need to be further improved and any safety concerns understood to provide the necessary impetus to go to the clinic.