Links between headache mechanisms and new medications.
A milestone in migraine (M) treatment was the discovery of the dramatic analgesic action of a nonanalgesic drug, ergotamine. The second step consisted in the identification of the prophylactic power of serotonin antagonists, particularly methysergide, in support of the serotonin theory of M. A growing number of drugs has widened the therapeutic resources in this area and at the same time has raised more and more complex and fascinating pathogenetic questions. According to the personal theory, pain in idiopathic headaches (IH) is the clinical expression of an automatism of transmission of painful signals along the neuroaxial sensory pathways. This automatism is in turn linked to a fault in the suprespinal pain modulating systems. This is a similar, but obviously not identical, situation to that of automatic pain transmission in organic deafferentation. As animal experiments have shown, the activation of the afferents may cause the retrograde (antidromic) release of substance P (SP) (and of the neurokinins related to it). This substance is devoid of algogenic capacity but endowed with a high capillary permeabilizing power, with consequent neurogenic edema (NGE) due to plasma overflow. The heavy and lasting edema provoked in both the forearm and the hand by injection of both SP and releasing histamine 48/80 b.w. into the humeral artery, is by no means painful, unlike that induced by injection into the superficial temporal artery (moderate urent pain), probably because of the greater sensitivity of the vascular structures of the head. It may be postulated that the repeated episodes of NGE may lead to a "sterile" phlogosis (neurogenic inflammation) which is capable of increasing and prolonging the pain in the periphery.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicolodi
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Interuniversity Centre, Florence University, Italy.
Sicuteri
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F
D003027:Cluster Headache / Q000188:drug therapy / Q000503:physiopathology; D004878:Ergotamine / Q000627:therapeutic use*; D006261:Headache / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology
D004878:Ergotamine