The role of serotonin and other neuroactive molecules in the physiopathogenesis of migraine: current hypotheses.

The study of the mechanisms of action of the triptan group of drugs has lar gely contributed to the progress made in the understanding of the physiopat hological processes that are possibly responsible for migraine. In this con text, two discoveries have been especially important: I) these anti-migrain e drugs are specifically recognized by three main types of serotonin recept ors (5-HT1B, 5-HT1D, and 5-HT1F), and 2) these receptors are present in the meninges, where they are expressed by both smooth muscle cells and/or endo thelial cells of the vascular wail and/or the perivascular trigeminal to be deleted axon terminals. These two findings have led to the most currently accepted physiopathogenic hypothesis, whereby the migraine attack would sta rt with an excitation of the perivascular trigeminal to be deleted fibers, which would then trigger the release of vasoactive peptides (substance P, c alcitonin gene-related peptide/CGRP) within the dura mater. Locally, i.e., in the dura mater in particular, these substances can provoke vasodilatatio n (CGRP) and plasmatic extravasation (substance P) with platelet lysis and mast cell degranulation, thereby leading to the release of algogenic substa nces that excite the neighboring trigeminal fibers, and this neurogenic inf lammatory response can progressivelly extend to the meninges as a whole. Th is reaction subsequently reaches the bulbar and thalamic nuclei and then th e sensory cortex, where it is integrated and expressed as migraine pain. Th e aim of this article was to report the main findings on endogenous substan ces (serotonin, peptides nitric oxide [NO] etc.) which appear to play a key role in this physiopathogenic sequence. (C) 2000 Editions scientifiques et medicales Elsevier SAS.