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.

Adult↗

PubMed1999

Chromosome 6p-encoded HLA-DR2 determination discriminates migraine without aura from migraine with aura.

Segregation analysis indicates that migraine without aura (MWoA) and migraine with aura (MWA) have multifactorial inheritance, but involved genetic and environmental factors are largely unknown. A controlled study was performed to assess the HLA-driven liability to migraine and to verify if the heterogeneity between MWoA and MWA is HLA-linked. Forty-five migraine patients (31 MWoA, 14 MWA) and 53 healthy blood donors as controls, coming from the same geographic area, were studied. Tissue typing was performed using the standard complement-dependent microlymphocytotoxicity technique for HLA Class I and by PCR-SSP (Sequences Specific Primers) typing for HLA Class II. Data emerging from the present study showed no altered distribution for HLA Class I A, B, C antigen frequency in migraine (MWoA, MWA) if compared to the control group. HLA Class II DR2 antigen showed a decreased frequency in MWA group if compared with both MWoA (p = 0.01) and control group (p = 0.039, RR = 0.21). These results seem to support the hypothesis of a protective role of DR2 antigen in MWA and provide additional basis for the proposed difference within MWoA and MWA.

Adult↗

PubMed1998

Primary Headache and Helicobacter Pylori.

H. pylori infection has recently been associated with various vascular disorders. The aim of this study was to investigate its role in primary headache, a pathology strictly associated with vascular alterations. A total of 200 subjects affected by primary headache were evaluated. H. pylori infection was diagnosed by the 13C urea breath test. Headache was classified in tension-type headache, cluster headache, and migraine with or without aura. Prevalence of H. pylori infection and gastrointestinal (GI) symptoms were evaluated. H. pylori infection was found in 40% of the patients; prevalence of migraine without aura was found to be significantly greater in infected patients. The positive group showed no significant differences in the prevalence of the GI symptoms evaluated. In 30 infected patients, it was assessed whether the eradication of the bacterium was able to reduce frequency, intensity, and duration of clinical attacks of headache. After eradication, clinical attacks of headache completely disappeared in 17% of patients. Moreover, intensity, duration, and frequency of headache attacks were reduced in 69% of the remaining subjects. In conclusion, H. pylori infection is common in primary headache; bacterium eradication appears to be related to a significant reduction in clinical attacks of the disease.

Journal Article↗

PubMed1998

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine.

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t0), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t1). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants or migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t0 vs. CF = 8.16, P < 0.01 and F = 16.2, P < 0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t1 vs. t0 P < 0.05, t = 3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t1 vs. t0 P < 0.01, t = -4.03), whereas a significant increase of nitrite in total cell extracts was detected (t1 vs. t0 P < 0.001, t = -6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.

Adult↗

PubMed1998

Helicobacter pylori infection and vascular diseases.

Helicobacter pylori infection has recently been associated to some organic functional vascular disorders and, both observational and interventional studies have been carried out. A correlation between Helicobacter pylori infection and ischaemic heart disease was first described in 1994. Recent data, moreover, indicate a role of the bacterium in some functional vascular disorders such as primary headache and primary Raynaud phenomenon; indeed, some patients following eradication of Helicobacter pylori showed a significant improvement in the manifestations of these diseases. The host immune response against the bacterium may play an important role in the pathogenesis of vascular disorders, probably through a chronic stimulation of the release of vasoactive substances, such as cytokines, prostaglandins and others. However, various confounding factors such as co-infections, genetic and immunological host-factors, different strains of Helicobacter pylori or other may influence the data. Well designed case/control and randomized interventional studies are still needed to assess the real role of Helicobacter pylori in vascular disorders.

Antibodies, Bacterial↗

PubMed1997

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

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.

Adult↗

PubMed1997

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 psychophysical 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.

Adult↗

PubMed1997

Peppers and pain. The promise of capsaicin.

Capsaicin, the most pungent ingredient in red peppers, has been used for centuries to remedy pain. Recently, its role has come under reinvestigation due to evidence that the drug acts selectively on a subpopulation of primary sensory neurons with a nociceptive function. These neurons, besides generating pain sensations, participate through an antidromic activation in the process known as neurogenic inflammation. The first exposure to capsaicin intensely activates these neurons in both senses (orthodromic: pain sensation; antidromic: local reddening, oedema etc.). After the first exposure, the neurons become insensitive to all further stimulation (including capsaicin itself). This evidence led to the proposal of capsaicin as a prototype of an agent producing selective analgesia. This perspective is radically different from previous 'folk medicine' cures, where the drug was used as a counter-irritating agent (i.e. for muscular pain). The new concept requires that capsaicin be repeatedly applied on the painful area to obtain the desensitisation of the sensory neurons. Following this idea, capsaicin has been used successfully in controlling pain in postherpetic neuralgia, diabetic neuropathy and other conditions of neuropathic pain. Furthermore, evidence indicates that capsaicin could also control the pain of osteoarthritis. Finally, repeated applications of the drug to the nasal mucosa result in the prevention of cluster headache attacks. On the basis of this evidence, capsaicin appears to be a promising prototype for obtaining selective analgesia in localised pain syndromes.

Analgesics↗

PubMed1997

Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic pathways.

A controlled study was done with the aim of assessing the efficacy of hyperbaric oxygen (HBO2) in cluster headache and of studying the possible influence of this therapeutic approach on serotonergic pathways. Fourteen patients, aged between 26 and 56 yr, suffering from the chronic form of cluster headache were treated with HBO2 (n = 10) or environmental air (placebo) ( n = 4) during the 15 sessions of exposure (lasting 30 min each) in the hyperbaric chamber. The influence of this procedure on serotonergic pathways of pain was monitored by means of study of serotonin binding to mononuclear cells before and after the treatment for both subgroups. All of the treated 14 chronic cluster headache patients completed the study. In the subgroup treated with the placebo, no particular modifications on the number of attacks and of analgesic consumption as well as no change in the specific binding curve of serotonin to mononuclear cells were observed, whereas in the subgroup treated with HBO2 the clinical effectiveness and the appearance of plateau in the binding curves indicated that the oxygen therapy could act through serotonergic pathways.

Adult↗

PubMed1996

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 be 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.

Adult↗

PubMed1996

Putative neuroimmunological mechanisms in cluster headache. An integrated hypothesis.

During the last decade, numerous studies have been carried out to explore the function of the immune system in cluster headache and the release of reciprocal informational molecules from pain-sensitive structures. These neuroimmunological findings in cluster headache syndrome, although carefully considered, have varied from genetic aspects (HLA antigens) to functional activity of the immune system (NK cytotoxicity), and from study of the receptor expression of classical neurotransmitters of pain (5-HT, histamine) on immunocompetent cells, to the study of cytokines with a potent pro-inflammatory activity (interleukin-1). Other aspects considered have ranged from the study of the effectiveness of substances possessing a wellknown activity on the immune system (prednisone, lithium carbonate) in shortening cluster attacks to the 5-HT receptor expression changes observed on a peripheral substrate (monocytes) after the administration of sumatriptan. Although this was an exciting area of pioneering research, we have always interpreted our findings cautiously. In summary, we now believe that the neuroimmunological aspects of cluster headache can be proposed as an integrative model and that this immunological mechanism could improve our understanding of the pathogenic basis for this still obscure disease.

Cluster Headache↗

PubMed1994

Pneumocystis carinii pneumonia in a patient with chronic obstructive pulmonary disease but no evident immunoincompetence.

Explore the source record for details and available documents.

Bronchoalveolar Lavage Fluid↗

PubMed1994

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

Capsaicin, when repeatedly applied to the nasal mucosa of cluster headache patients, has been shown to prevent the occurrence of pain attacks. In order to investigate the mechanism of the drug's action, we evaluated the effect of repeated nasal application of capsaicin on the contents of sensory fibres immunoreactive to substance P and CGRP in the rat nasal mucosa. Further, considering the possible involvement of the cerebral circulation, we verified the effect of a single application of capsaicin on the blood flow velocity of the internal carotid and middle cerebral arteries (of both sides) and the basilar artery, in a group of healthy humans. The measurements were taken using Doppler devices. In order to verify the reproducibility of therapeutic effect of capsaicin, we carried out a 2-year follow-up study on patients affected by cluster headache (17 by episodic form, 8 by chronic form) who responded positively to the first treatment with capsaicin. During this period they were treated again with capsaicin in case of re-occurrence of symptoms. Capsaicin depletes the fibers immunoreactive to substance P and CGRP in the rat nasal mucosa. In the healthy controls, a single application induced vasodilation in the internal carotid, whereas middle cerebral arteries and basilar artery were narrowed. The results of the follow-up study, demonstrates that in 65% of the patients, the beneficial effect of capsaicin was again present when the treatment was repeated. In the chronic patients the therapeutic effect was always transitory (lasting, at maximum one month).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1994

Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan.

The double-label flow cytometric analysis of peripheral serotonergic pathways of migraine and cluster headache on a monocyte model has been used to evaluate the activity of drugs with a selective activity on central vascular 5-HT1D receptors, such as sumatriptan, ergotamine and ondansetron. The results indicated that sumatriptan and ergotamine progressively increase the peripheral expression of 5-HT (5-hydroxytryptamine, serotonin). The increase obtained in migraine after ergotamine is more evident than that obtained in cases of cluster headache. Ondansetron produced a moderate increase in serotonergic expression only in cluster headache. The events that occur at intracranic neural and vascular level may cause the described changes of 5-HT expression on the monocyte model as an indirect, reflective, peripheral registration of central serotonergic variations during headache attack as well as during the drug-sustained recovery phase.

Adult↗