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Biomedical subjects

P Martelletti

Publications and source records attributed to P Martelletti.

At least 19 recordsLinked to original sources
PubMed2004

Measure of negative impact of migraine on daily activities, social relationships and therapeutic approach.

The study has been conducted in 9 European countries, interviewing 200 women in each country, aged 18-35, in fully working or studying period, to get a total of 1810 people. Migraine or severe headache was recognised and patients were studied to understand their behaviour. The features and severity of headache, the use of different drugs, the relationship between physicians and patients, the disability during attacks, the psychological aspects and the feeling of impotence that migraine patients experienced during their lives, are analysed and reported.

Activities of Daily Living↗
PubMed2000

Linked activation of nitric oxide synthase and cyclooxygenase in peripheral monocytes of asymptomatic migraine without aura patients.

Many reports indicate that nitric oxide (NO) could be involved in migraine without aura (MWA), an extremely diffuse clinical event. Since monocyte may be a relevant source of NO, we analysed monocyte activation in MWA patients, in a period in which they were free of symptoms. NO basal production by MWA peripheral monocytes was significantly higher than in healthy subjects (91.25+/-8.6 microM/10(6) cells vs. 22.6+/-3.2 microM/106 cells). Interestingly, even the release of prostaglandin E2 (PGE2), was higher in MWA patients than in healthy subjects (3137+/-320 pg/10(6) cells vs. 1531+/-220 pg/10(6) cells). The incubation of monocytes from healthy subjects and MWA patients with N-nitro-L-arginine methyl ester caused a marked decrease of both NO and PGE2 release. We hypothesise that NOS and cyclooxygenase pathways in monocytes are linked and are, in MWA patients, up-regulated, even in a symptoms-free period. NO and PGE2 hyperproduction could therefore be involved in the neurovascular modifications leading to migraine attacks.

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

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↗
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

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

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

Function of the peripheral serotoninergic pathways in migraine: a proposal for an experimental model.

We propose a model for assessing the function of 5HT receptors in migraine by evaluating their expression on monocytes by means of double-labeling fluorocytometry (CD14-positive cells FITC-labeled). This model demonstrates that during headache induced in migraine without aura sufferers given isosorbide dinitrate followed by sumatriptan treatment 5HT expression on monocytes progressively increases. This increase may be due to the activation of 5HT turnover and to the increased availability of 5HT displaced by sumatriptan from cerebrovascular receptors during head pain.

Adult↗
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↗
PubMed1993

Serum interleukin-1 beta is increased in cluster headache.

We measured serum interleukin-1 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.

Adult↗
PubMed1993

Is the unresponsiveness to sumatriptan in cluster headache related to an alteration in the 5-HT receptors?

It is well established that cluster headache shows impaired functions at the neuroimmunomodulatory system level. Defects in the expression of receptors for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, an agonist activity for 5-HT1D receptor, truncates cluster headache attack in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients which are non-responders to sumatriptan could present a block in their 5-HT receptor expression possibly due to specific autoantibodies for this receptor site.

Adult↗