Mario Giacovazzo

Oral Rizatriptan Versus Oral Sumatriptan: A Direct Comparative Study in the Acute Treatment of Migraine

Rizatriptan is a potent, oral, 5‐HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double‐blind, triple‐dummy, parallel‐groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P=0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P≤0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P=0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain‐free response (P=0.032), reduction in functional disability (P=0.015), and relief of nausea at 2 hours (P=0.010). Significantly fewer drug‐related clinical adverse events were reported after rizatriptan 10 mg (33%, P=0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.

Hyperbaric oxygen therapy in cluster headache

Preliminary reports have shown that hyperbaric oxygen (HBO) interrupts cluster headache (CH) attacks. In the present study, 6 of 7 patients with episodic cluster headache who were treated with hyperbaric oxygen experienced an interruption of the attack. In 3 of 6 responders the florid period of the cluster headache was interrupted. The other 3 patients remained without pain attacks for a period lasting from 3 to 6 days. In 6 different patients, a placebo treatment had no effect. The present findings clearly indicate that hyperbaric oxygen has not only a symptomatic effect on a single attack of cluster headache, but it also could prevent the occurrence of subsequent attacks.

Alteration of central excitation circuits in chronic headache and analgesic misuse.

Central excitatory circuits could be involved in the pathophysiology of pain; particularly, the genesis of chronic pain. The “second pain” is the sensation that follows the initial pain after an appropriate nociceptive stimulus. The second pain is amplified by repeating the stimulus after brief intervals (temporal summation). This phenomenon is the psychophysicaI correlate of the excitatory pain circuits. The temporal summation of the second pain was evaluated in four groups of subjects: one group affected by migraine without aura, one by episodic tension headache, one by chronic daily headache, and a group of healthy subjects. A percutaneous electrical shock was used as the nociceptive stimulus. The intensity of the second pain was significantly greater in the group of patients with chronic headache in comparison with the other groups. The patients with chronic headache were subdivided into three groups on the basis of their clinical history: a group with transformed migraine; a group with chronic headache ab initio a form related to the first one; (both groups suffered from chronic daily headache with a frequent superimposition of episodes of migraine attacks) and the third group consisted of patients with chronic tension headache. The temporal summation of the second pain was altered in the first two groups. The patients with chronic migraine abused ergotamine given as a symptomatic drug. Those who were able to discontinue this drug were retested and reported a decrease of the second pain in comparison to the previous measurements. The results of the present study indicate that central excitatory circuits could be involved in the mechanism leading to the development of chronic daily headache.

Tumor necrosis factor gene polymorphism in migraine

Objective.—To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura.

Inhibition of intercellular adhesion molecule-1 (ICAM-1), soluble ICAM-1 and interleukin-4 by nitric oxide expression in migraine patients

Abstract The mechanisms of the postulated ”sterile” inflammation in migraine were studied utilizing flow cytometry (intercellular adhesion molecule 1, ICAM-1; interleukin-1 receptor, IL-1R) and enzyme-linked immunosorbent assay (soluble intercellular adhesion molecule 1, sICAM-1; interleukin-4, IL-4). Twenty patients suffering from migraine without aura, 20 healthy subjects, and 10 patients suffering from episodic tension headache were selected. All of the migraine patients were studied during a migraine crisis experimentally induced by the administration of isosorbide dinitrate (a nitric oxide donor), and 10 out the 20 were also studied during a spontaneous migraine attack. A sharp decrease in the expression of ICAM-1 (F=5.09, p<0.001 and F=2.46, p<0.05, respectively), sICAM-1 1 (F=6.21, p<0.0001 and F=3.99, p<0.007, respectively) and serum IL-4 (F=6.23, p<0.001 and F=3.64, p<0.01, respectively) were observed in experimentally induced and spontaneous migraine attacks. There was no change with respect to IL-IR 1 receptor expression values. The two control groups, tested with the same experimental procedure, showed no changes in ICAM-1 and IL-1R or in in sICAM-1 and IL-4. Our data suggest that migraine patients are more sensitive to exogenous NO than controls. In addition, our results indicate that experimental migraine crisis, induced by an NO donor, is mediated by the inhibition of IL-4 and subsequently of ICAM-1. It is likely that the described ICAM-1 downregulation inhibits during a migraine attack the critical step of transendothelial migration into the cerebral tissues of activated leukocytes, as proposed in the ”sterile inflammation” hypothesis.

Capsaicin-sensitive sensory neurons in cluster headache: pathophysiological aspects and therapeutic indication.

SYNOPSIS

Serum interleukin-1 beta is increased in cluster headache

We measured serum interleukin-I beta (IL-1 beta) in 24 episodic cluster headache (CH) patients and 45 normal controls using a specific ELISA method. There was an increase in IL-1 beta in all CH patients compared to controls. IL-1 beta was further increased during the ictal phase of CH compared to patients between attacks and normal individuals. Between attacks, IL-1 beta was also significantly increased compared to controls. We suggest that these results represent an activation of the immune system in CH.

Low plasma testosterone levels in cluster headache

Serum levels of various hormones have been estimated in cluster headache and non-cluster headache controls. Cluster headache patients were studied prior to, during, and after attack. During the cluster phase, plasma testosterone levels were low, whereas levels were within the reference limits in the remission period of episodic cluster headache. LH levels were within reference limits. Normal values were also found in control patients with non-cluster headache. It is suggested that a decrease of plasma testosterone levels in episodic cluster headache should be viewed in context with disordered REM sleep in cluster headache.

Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the ‘aura’ phenomenon.

Effect of Hyperbaric Oxygen on the Immunoreactivity to Substance P in the Nasal Mucosa of Cluster Headache Patients

Exposure to hyperbaric oxygen has been shown to the effective in cluster headache, but the mechanism of the action is still not clear. Primary nociceptive neurons, containing neuropeptides such as substance P and particularly those innervating the nasal mucosa, could be involved in the pathogenesis of cluster headache. The present study evaluated the effect of an exposure to hyperbaric oxygen on the content of substance P in the nasal mucosa of patients affected by cluster headache. The results were compared with those observed in another group of cluster headache patients who underwent a placebo procedure. The samples of nasal mucosa were analyzed by immunocytochemical methods. A qualitative analysis of the slides was carried out by an operator under “blinded conditions.” A marked decrease in the content of immunoreactivity for substance P was found in the patients exposed to hyperbaric oxygen. The decrease was statistically significant when compared with the findings of the placebo procedure. The results of the present study indicate that an influence on the content of peripheral neuropeptides could be involved in the mechanism of action of the beneficial effect of hyperbaric oxygen in cluster headache.