Rôle du récepteur 5-HT2A de la sérotonine dans la douleur neuropathique périphérique

Serotonin (5-HT), one of the main neurotransmitters of the nervous system, is involved in the transmission and control of pain at all levels. In peripheral tissue, lesions trigger platelets to release 5-HT which leads to local inflammation. In the spinal cord, where it is the first mediator transmitting nociceptive information, 5-HT, which arises from the nucleus raphe magnus, modulates cell activity and thus ensures fine tuning of information transmission to the central nervous system. The action of 5-HT is however very complex due to the large number of targets, receptors and responding cells.We describe here the fact that the localization of one of the 5-HT receptors, 5-HT2A, in peripheral and spinal neurons, is in agreement with an important role for this receptor in the transmission of pain. An electron microscope study has demonstrated that 5-HT affects this receptor via a paracrine mechanism. After a brief recall of the available data establishing the fundamental role of the peripheral 5-HT2A receptor in inflammatory pain, we examine more recent data obtained from animal models and clinical medicine, showing that the 5-HT2A receptor is also implied in neuropathic pain. We show that this effect is observed in both the peripheral system and in the spinal cord.These results suggest that specific antagonists of the 5-HT2A receptor, at least after peripheral administration, could have a beneficial effect for the treatment of neuropathic pain, which, in terms of therapeutic efficacy, remains one of the most challenging types of pain.