Abstract
The serotonin theory of migraine (M) we proposed in the seventies indicated a pivotal role of serotonin in mechanism of M (Sicuteri et al., 1974). The analgesizing role of the indolamine was then stressed (Yaksh et al., 1977, Fields and Anderson, 1978). We began to study the serotonin mechanism in primary headache in the sixties. At that time we hypothesized that serotonin could have had a mainly excitatory effect on polymodal receptors. Their serotonin-mediated activation was supposed to evoke headache pain. This theory re-emerged in recent years, in spite of the fact that substantial data showing have been obtained indicating that M, as well as other related primary pains, are caused chiefly by a failure of serotonergic analgesizing systems in the CNS (Sicuteri et al., 1973, Sicuteri et al, 1978, Del Bianco et al., 1982, Rajiv et al., 1989, Lance, 1992). As a matter of fact, serotonin is a transmitter characterized by a double-faceted effect, in that it is a pain-sensitising agent at the periphery (by acting on polymodal receptors) (Sicuteri et al., 1965), whereas it displays an evident antinociceptive effect by activating serotonergic analgesizing systems in the CNS. The centrally mediated analgesizing effect seems to largely overcome the pain-sensitising peripheral effect of the amine (Kimball et al., 1960). Among the more convincing outcomes supporting this assumption we can cite the effect of fenclonine, which we tested first in the late sixties (Sicuteri et al., 1973, Sicuteri et al., 1978). Fenclonine is a potent and irreversible inhibitor of tryptophan (Trp) hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. When fenclonine is administered, enzyme activity is reduced in both cell bodies and nerve terminals.
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Nicolodi, M., Sicuteri, F. (1996). Eosinophilia Myalgia Syndrome. In: Filippini, G.A., Costa, C.V.L., Bertazzo, A. (eds) Recent Advances in Tryptophan Research. Advances in Experimental Medicine and Biology, vol 398. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0381-7_54
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