RESPONSIVENESS OF THE TRIGEMINOVASCULAR SYSTEM TO NITROGLYCERINE IN CLUSTER HEADACHE PATIENTS

Nitroglycerine is known to induce a headache attack in cluster headach e patients, which is indistinguishable from a spontaneous attack. It h as recently been suggested that a release of calcitonin gene-related p eptide (CGRP) from peripheral terminals of trigeminal nociceptive neur ons, which supply cephalic blood vessels, underlies symptoms of cluste r headache. The aim of this study was to investigate whether the provo cative action of nitroglycerine in cluster headache is due, at least i n part, to activation of the trigeminovascular system. Nineteen subjec ts suffering from episodic cluster headache participated in the study. Eleven of them were in an active period whilst the others were in rem ission at the time of the study. CGRP-like immunoreactivity (CGRP-LI) was measured in blood samples from the extracerebral circulation befor e and after the sublingual administration of nitroglycerine. Baseline CGRP-LI plasma levels were higher (P < 0.05) in the patients who were in an active period. Only in these patients did nitroglycerine induce an attack, which was preceded by a latent period with a mean duration of 27+/-3 min. When compared with the baseline, a significant (P<0.01) increase in plasma CGRP-LI was detected at the peak of the provoked a ttack; no such increase was detected during the latent period, or at t he onset of the attack. The results of this study suggests that the pr ovocative action of nitroglycerine in cluster headache is due, at leas t in part, to activation of the trigeminovacular system. This mechanis m seems to be slow and unrelated to the well-known rapidly occurring v asodilator effects of the drug. Finally, activation of the trigeminova scular system only occurs in those patients already in an active clust er headache period who also have high basal CGRP-LI plasma levels. Thi s suggests that a hyperactivity of trigeminal nociceptive fibres could make the trigeminovascular system of these patients sensitive to the triggering action of nitroglycerine.