21:T413,The trigeminal ganglion was activated, in humans by thermocoagulation as part of the treatment of trigeminal neuralgia and in cats by electrical stimulation, and blood samples were taken from the external jugular vein for estimates of plasma levels of substance P and calcitonin gene-related peptide (CGRP). In those patients who were noted at the time of coagulation to have flushed there were marked elevations of the local (cranial) levels of both peptides. However, in the nonflushing patients no changes in the peptide levels were observed. Parallel experiments in the cat revealed that the levels of substance P-like and CGRP-like immunoreactivity were increased during electrical stimulation of the trigeminal ganglion. The observation of elevation of substance P-like and CGRP-like immunoreactivity after activation of the nociceptive afferent system of the head provides new insights into a putative role of peptides in the pathophysiology of migraine and cluster headache, and suggests new areas of possible therapeutic intervention.22:T40d,Studies on man and lower animals have shown that the cranial blood vessels are pain-sensitive structures, capable under special circumstances of giving rise to headache.¹The distention of cerebral arteries is primarily responsible for the headache produced by certain chemical agents, of which histamine is representative;²the headache associated with septicemia and fever is in the same category.³It has been shown that the afferent fibers from the pain-sensitive cerebral arteries above the tentorium enter the brain stem primarily through the fifth cranial nerve, whereas the fibers from the arteries below the tentorium enter the nervous system chiefly through the upper cervical nerves.⁴The distention of certain branches of the external carotid arteries is chiefly responsible for migraine headache and the headache associated with arterial hypertension.⁵ Thus, data about the great variety of headaches resulting from distention of cranial arteries are specific, but there is

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