Unmasking Latent Dysnociception in Healthy Subjects

Abstract

SYNOPSIS Headache is the most common side effect of nitroglycerin, administered for angina pectoris. Two phases can be distinguished in nitroglycerin‐induced headache: the first phase (immediate headache), a mild sensation of temporal pulsating pain, can be due, at least in part, to the vasodilation provoked by nitroglycerin; the second phase (delayed headache), an increasing pain, possibly with nausea and vomiting, lasting even for a number of hours, is independent from the vasomotility, since it arises and persists when all vasomotor and metabolic nitroglycerin‐induced changes are over. The present investigation demonstrates that healthy subjects, neither suffering from idiopathic headache nor with a family headache history, never complain of delayed headache after nitroglycerin; healthy subjects not suffering from headache but who have one or both parents suffering from migraine, exhibit the delayed long‐lasting headache in 28.6% of cases; finally, 66.7% of their migrainous parents complain of the delayed long‐lasting headache after nitroglycerin. The following conclusions can be drawn: nitroglycerin‐induced delayed headache 1) is not a true side effect of nitroglycerin, since it is never present in healthy subjects; 2) is peculiar to migraine sufferers: or 3) is an index of migraine predisposition, as it may be present in healthy subjects, but only if they have one or two migrainous parents. The features of nitroglycerin‐induced delayed headache suggest an analogy with the phenomenon of overreaction, a painful and exaggerated response (in latency, intensity and duration) to a stimulus, that is the most typical aspect of central pain. In nitroglycerin‐induced delayed headache, which shows close similarities to the spontaneous attack of migraine, the trigger stimulus could be the moderate immediate headache which is probably correlated with the vasodilation provoked by nitroglycerin.

Nitric Oxide-Related Drug Targets in Headache

“…1). This experiment confirmed previous observations by Sicuteri et al 31 that migraine sufferers have an immediate, as well as delayed headache, and that the latter, according to the patients, was indistinguishable from their spontaneous migraine attacks. The super sensitivity to GTN in migraine sufferers could be due either to the trait or state of migraine.…”

“…In older literature, no distinction was made between the immediate headache after administration of GTN and the headache that occurred in migraine patients long after the administration of GTN. 1,30 Sicuteri et al 31 focused on this issue and suggested that migraine sufferers and first-degree relatives of migraine sufferers: 1) were more sensitive to GTN than normal controls; and 2) developed a delayed headache that was migraine-like. Because of a lack of explicit diagnostic criteria for migraine at the time, it was not possible to analyze whether the headache did or did not fulfill diagnostic criteria for migraine.…”

Sumatriptan Relieves Migrainelike Headaches Associated With Carbon Monoxide Exposure

“…[24][25][26][27][28][29] Several studies report that migraine patients are unusually sensitive to acute NTG-induced headache and delayed onset migraine attacks. 25,[30][31][32] Delayed NTG-induced headache also occurred in subjects without migraine, but with a positive family history. This occurred in 28.6% of patients with a positive family history and in no patients without a positive family history.…”

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

“…Nitroglycerin (NTG)-administration is a model of migraine, being able to generate migraine attacks in migraineurs (Sicuteri et al, 1987), and trigger activation and sensitization in the trigeminal system (Di Clemente et al, 2009). It is also well-known, that NTG-a nitric oxide donor (NO)-can initiate trigeminal activation and sensitization in animals as well (Pardutz et al, 2000;Tassorelli and Joseph, 1995).…”