Platelet Monoamine Oxidase Activity in Female Migraine Patients

Platelet monoamine oxidase activity (MAO) in a group (n = 17) of white, female migraineurs during an acute migraine attack was similar to both the values obtained for the same group of patients two to three weeks after the headache episode (pain-free period) and to the results obtained for a group (n = 18) of sex and race-matched, age-comparable, drug-free healthy volunteers (blind study; substrate p-tyramine, 38.7 +/- 5.7, 41.9 +/- 8.8 and 43.0 +/- 3.4 or p-methoxybenzylamine, 178.9 +/- 11.3, 177.2 +/- 6.9 and 181.0 +/- 9.7 nmole/hr/10(9) platelets +/- SD respectively). With each patient serving as its own control, MAO activity during the migraine episode and when pain-free failed to show a significant trend. Neither a number of other medical conditions nor the use of several medications appeared to significantly influence our results. The present work, while dealing only with a small but well defined patient population, argues against the possible usefulness of platelet MAO activity as a biological marker for migraine headaches.     

Platelet Antibodies in Patients With Migraine

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We, therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.5% of patients with migraine without aura, 7.6% of patients with migraine with aura, and in 7.5% of controls; IgM antibodies were found in 11.9% of patients with migraine without aura, in 30.8% of patients with migraine with aura, and in 13.1% of controls. Most antibodies ware directed against glycoprotein complexes IIb-IIIa (fibrinogen receptor) or IB-IX (thrombin receptor). Two patients with migraine without aura but no patient with migraine with aura nor any control subject had IgG antibodies of unknown specificity. One patient (2.4%) with migraine without aura and two patients (7.7%) with migraine with aura, as well as 2 controls (1.9%) had IgM antibodies not further specified. The differences in frequency of platelet antibodies of known or unknown specificity in patients with migraine without aura and migraine with aura and controls were not statistically significant. Therefore, our data do not support the hypothesis of a pathophysiologically relevant autoimmune reaction against platelet serotonin receptors in the majority of patients with migraine. We can not exclude the occurrence of antibodies against neuron-specific serotonin receptors.     

Platelet Fibrinogen Receptors in Migraine Patients

SYNOPSIS
In order to determine the platelet characteristics responsible for aggregation, the number and apparent dissociation constant (K D aPP ) of fibrinogen receptors were determined in 12 women with common migraine. The studies were performed by the use of 125 -fibrinogen. The patients were assessed in headache-fee intervals. The mean number of platelet fibrinogen receptors exposed in migraine patients was significantly higher than those obtained in healthy controls (p<0.05). The (K D aPP ) in migraineurs was about three times lower than in the controls (p<0.02). The results indicate that both the number and affinity of fibrinogen receptors or platelets are increased in migraine patients. The authors conclude that this phenomenon may be responsible for the increased number of circulating platelet aggregates in migraine patients and for the prevalence of various kinds of strokes during migraine attacks.     

Platelet Lipid Composition in Human Migraine

SYNOPSIS
Fatty acid profiles were determined in platelets of 21 patients suffering from Classical Migraine and these results were compared with those obtained in a control group of 24 healthy individuals. Cholesterol levels and the cholesterol/phospholipid ratios of 4 of the migraine patients were investigated and compared with values obtained from 4 age-matched control persons.
No significant differences could be detected between the fatty acid profiles of the migraine and control groups, Analysis of the cholesterol content and the cholesterol/phospholipid ratio of the platelets revealed no significant differences between the two groups.
Freeze-fracture electron microscopy of the platelet membranes of the two groups revealed no striking differences in the protein distribution and environment in the migraine condition.
We conclude that the membranes of platelets of migraine-suffering and control individuals have a similar composition, the symptoms of this disorder thus being mediated by other differences between the platelets.     

Platelet Norepinephrine and Serotonin Balance in Migraine

Platelet serotonin (5 hydroxytryptamine, 5-HT) and norepinephrine (NE) were measured in common and classic migraine patients and healthy controls. Common migraine sufferers had high NE levels and a low 5-HT/NE ratio. Classic migraine patients had a high 5-HT level and a high 5-HT/NE ratio. The data suggest disparate NE and 5-HT metabolism between common and classic migraine.     

Migraine Is Not a Platelet Disorder

SYNOPSIS
The platelet theory of migraine causation predicts that drugs inhibiting platelet activation will be effective in migraine prevention, but the literature indicates that this is only partly the case. Conversely, therapy achieving clinical benefit should be associated with reduced platelet activity. To test this concept, the β-adrenergic blockers propranolol (non-selective), metoprolol (β₁-selective) and Li-32468 (β₂-selective) were used in migraine therapy with assessments of platelet aggregation and release, plasma thromboxane A₂ (measured as thromboxane B₂) and clinical response.
Between propranolol and Li-32468, there was lack of correlation of clinical with platelet effects. Propranolol and metoprolol, whose established efficacy in migraine prophylaxis was reflected here, actually had opposite effects on platelet activity, which was increased with the former and inhibited by the latter. Yet both drugs gave elevated thromboxane B₂ levels.
In view of this complete dissociation between drug effects on platelets of migraineurs and symptoms of migraine, the platelet theory of migraine causation is untenable.     

Migraine and Cluster Headache: Links Between Platelet Monoamine Oxidase Activity, Smoking and Personality

SYNOPSIS
The incidence of smoking in a group of male cluster headache patients (95%) was significantly (P<0.001) greater than in a matched group of male migrainous patients (26%). Both groups had significantly lower platelet monoamine oxidase activity than controls. This finding may be connected genetically with certain personality characteristics, including predisposition to smoke. It is possible that migrainous patients smoke less than those with cluster headache because the process of smoking has a greater tendency to provoke their headache attacks.     

Migraine Patients Show Increased Platelet Vasopressin Receptors

This study was designed to investigate vasopressin receptor status (B_max and K_d) on platelets, vasopressin plasma levels, and vasopressin-induced platelet aggregation in migraine patients (21 females and 6 males) during a headache-free interval and in a matched control group. In the migraine group, B max was significantly higher ( P = 0.02) at 53.9 ± 20.6 fmol/mg than in the control group (36.8 + 21.0 fmol/mg). A correlation between B_max and high or low sensitivity to vasopressin as an aggregator was evident in the control group, but not in the migraine group. No differences in K_d or in plasma levels of vasopressin between the migraine and control group were apparent. Men in both groups were much less sensitive to vasopressin as a platelet aggregator than were women ( P < 0.01). Whether the higher B_max in the migraine group is a reflection of temporarily higher vasopressin levels during headache or reflects a primary increase in sensitivity to vasopressin, remains to be clarified. The higher sensitivity of platelets (as a model for vessel wall receptors) from women may indicate why many more women than men suffer from migraine. Since the B_max of the vasopressin receptor on platelets from migraine patients is increased compared to controls, treating migraine headache with vasopressin may deserve more attention.     

The Platelet Release Reaction During Migraine Attacks

SYNOPSIS
An investigation is reported of serum levels of Beta Thromboglobulin (BTG), a platelet release reaction specific protein, and the stable metabolites of thromboxane B2 and prostacyclin during and between migraine attacks, and in age and sex matched controls.
The level of BTG in plasma from controls was 61.3 ngml (± 26.15), in patients during migraine attacks 127.69 ngml (± 82.8) whilst between attacks the level was 69.06 ngml.
No changes were observed in the levels of the stable metabolite of thromboxane B2 and prostacyclin.
The significant rise in BTG (p = < .02) during migraine attacks indicates that the platelet release reaction occurs during the headache phase.     

Platelet Gamma-Aminobutyric Acid Levels in Migraine and Tension-Type Headache

Gamma-aminobutyric acid (GABA) levels in platelets were measured in 19 patients with migraine (7 males and 12 females, average age: 36.5 years) and 27 patients with chronic tension-type headache (TH; 9 males and 18 females, average age: 48.9 years). Twenty-one normal healthy volunteers composed the control group (11 males and 10 females, average age 34.9 years). The GABA levels in platelets were determined using high performance liquid chromatography with fluorescent detection (HPLC-FC). The GABA levels in platelets were 30.8 +/- 11.7 pmol/10(9) platelets (mean +/- S.D.) in the patients with migraine, 43.1 +/- 11.8 pmol/10(9) platelets in the patients with TH and 34.7 +/- 8.1 pmol/10(9) platelets in the healthy controls. The platelet GABA levels in the patients with TH were significantly higher than in the migraine patients and the healthy controls (p less than 0.05). The possible role of GABA in headache is discussed. We consider that TH may be a state of neuronal hyperexcitability similar to migraine and that GABA in the platelets of patients during TH attacks may be elevated to counterbalance it. Alternatively, we suggest that the rise of GABA levels in platelets is related to emotional factors, such as depression, in the TH patients. Further studies must be undertaken concerning the relationship between platelet GABA levels and headache.     

Increased 11-dehydrothromboxane B 2 in Migraine: Platelet Hyperfunction in Patients with Migraine during Headache-free Period

SYNOPSIS
Several disturbances in platelet function have been reported in migraine and tension-type headache (TH). The plasma 11-dehydrothromboxane B ₂ (11-dTXB ₂ ) is free from artifactual increase during blood sampling, and it can be a reliable indicator of thromboxane A ₂ (TXA ₂ ) production in vivo. TXA ₂ is a very potent proaggregatory and vasoconstrictory metabolite formed in the platelets. We investigated plasma 11-dTXB ₂ and 5-hydroxytryptamine (5-HT) levels in patients with migraine during headache-free periods and in patients with chronic TH. The mean value of plasma 11 -dTXB ₂ levels in migrainous patients was significantly higher than those in TH patients and healthy controls. The mean value of plasma 5-HT levels in TH patients was significantly lower than those in migrainous patients and healthy controls. There was no correlation between plasma 11-dTXB ₂ levels and plasma 5-HT levels in any group. The results suggest the existence of continuous platelet activation in migrainous patients.     

Platelet Membrane Lipid Composition and the Frequency of Migraine

SYNOPSIS
A variety of evidence associates abnormalities in platelet function with the development of migraine. Given the pivotal role of platelet membranes in these functions, it was proposed that migraine patients have abnormalities in their platelet membrane composition. To examine this hypothesis, platelet membrane lipid composition was analyzed in 16 migraine patients and 10 control subjects. The content of phosphatidylcholine, the amount of arachidonic acid in phosphatidylcholine, and the amount of unsaturated fatty acids in most phospholipids were significantly increased in patients with infrequent migraine as compared to controls or patients with frequent migraine. These results suggest that membrane lipid composition may play a role in the frequency and severity of migraine attacks.     

Platelet Activation and Migraine: A Study with Flunarizine

SYNOPSIS
Although in common and classic migraine there is platelet activation both during painful attack and headache-free periods, the role of platelets in migraine pathogenesis is not yet understood. Therefore, in order to investigate the relationship between platelets and migraine pathogenesis, β-thromboglobulin (β-TG) and platelet factor four (PF₄), both platelet-specific alpha granule proteins, were assayed in a group of patients with classic and complicated migraine before and after administration of an anti-migraine drug, flunarizine, at a dose of 10 mg/daily. Blood samples for β-TG and PF₄ assay were collected for ten days in which the patients were headache-free. β-TG and PF₄ plasma levels were elevated in all patients in comparison with control subjects. The patients with complicated migraine showed the highest plasma values. During flunarizine treatment β-TG and PF₄ levels persisted elevated in all patients, although a slight decrease of β-TG plasma levels was observed. This data confirmed, as our previous works, that classic migraine is characterized by platelet activation "in vivo," but that this may not be strictly related to migraine pathogenesis.     

Platelet Alpha2-Adrenoceptor Binding in Migraine

SYNOPSIS
Platelet alpha 2 -adrenoceptor binding was determined in ten migraine patients and sixteen healthy controls using (³H)-yohimbine as radioligand. The mean value of maximum binding (^Bmax ) in the migraine patients was 133 ±55 binding sites/ platelet which is significantly lower than that of 217 ± 76 binding sites/platelet in controls (p<0.01). There was also a significant difference in the mean dissociation constant (K_D ); 2.05 ± 0.44 nM in migraineurs and 2.98 ± 1.15 nM in controls (p<0.05). Platelet alpha 2 -adrenoceptors may constitute valid models for certain characteristics of alpha 2 -adrenoceptors in the brain. An alteration in platelet alpha₂ -adrenoceptor binding may thus reflect similar alterations in central alpha₂ -adrenoceptors. It is also discussed whether the alpha₂ -adrenoceptor abberrations are intrinsic to migraine or a result of endogenous and/or pharmacologically induced modulation.