Muscle contraction headache and migraine:Platelet activation and plasma norepinephrine during the cold pressor test

For clarification of possible platelet activation in migraine and chronic muscle contraction headache (MCH) under stress, plasma platelet factor 4 (PF4), norepinephrine (NE), and free fatty acids (FFA) were investigated during the cold pressor test. Both PF4 and NE increased significantly, whereas FFA showed no remarkable changes. The increases of PF4 in MCH and migraine during this test were significantly greater than in healthy controls. The increase of PF4, however, was independent of NE increase and FFA changes. On the other hand, we observed decreased NE levels in both MCH and migraine, which might suggest peripheral sympathetic hypofunction. The platelets of MCH or migraine patients seem to be impaired, and the impairment may be caused by continuous sympathetic hypofunction. The behaviour of the above three substances in MCH was similar to that in migraine throughout the present study.     

Platelet activity in cluster headache

Platelets are known to be activated in common or classic migraine both during the attack and in headache-free periods. Platelet behavior is less well known in cluster headache. We have investigated beta-thromboglobulin (beta-TG) and platelet factor four (PF4) plasma levels, markers of in vivo platelet activation, in patients during remission and during bouts of cluster headache with and without pain. The results indicated that statistically significantly higher levels of beta-TG and PF4 occur in the patients during the remission period when compared with the control subjects. Such high levels seemed to persist between paroxysmal episodes in cluster periods. However, during the attacks of cluster headache beta-TG and PF4 plasma levels decreased by 42% and 50%, respectively, in comparison with plasma concentrations measured outside of attack. Thus, although platelet activation also occurs in patients with cluster headache, the attack as such seems to be characterized by a marked reduction in platelet activation.     

Pupillary sympathetic hypofunction and asymmetry in muscle contraction headache and migraine

Pupillary autonomic dysfunction and right-left differences were investigated in muscle contraction headache (MCH) and migraine, by means of biocular infrared videopupillography (biocular Iriscorder). The study was performed on 36 patients with MCH or migraine and on 23 healthy controls. The pupillary area before light stimuli and maximum dilatation velocity of pupils, in MCH patients and migraineurs, showed significant differences from those of controls. Pupillary asymmetry was observed in both headache categories. The behavior of MCH pupils to light stimuli under dark conditions was rather similar to that of migraine pupils. Both pupillary sympathetic hypofunction and subtle anisocoria were present not only in patients with migraine but also in those with MCH.     

Platelet superoxide dismutase in migraine and tension-type headache

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.     

Pupillary functional asymmetry in patients with muscle contraction headache

Twenty-five patients with 'muscle contraction headache' (MCH) underwent tyramine pupillary tests, and 15 of them also underwent physiologic pupillary tests and cold pressor tests. Twenty healthy controls underwent tyramine pupillary tests, physiologic pupillary tests, and cold pressor tests. In the tyramine pupillary tests and the physiologic pupillary tests, the controls showed a symmetric mydriasis. In contrast, MCH patients showed asymmetric mydriasis after tyramine instillation and in the physiologic pupillary tests. In the cold pressor tests MCH patients reacted in the same manner as the controls. It is suggested that MCH patients have pupillary sympathetic imbalance. The role of this imbalance in the pathogenesis of MCH remains uncertain.     

Platelet levels of dopamine are increased in migraine and cluster headache

OBJECTIVE: To measure plasma and platelet levels of dopamine in patients with migraine with aura, migraine without aura, and cluster headache. BACKGROUND: Clinical, genetic, and pharmacological evidences suggest that an abnormality of dopaminergic system plays a role in migraine pathogenesis. Direct evidence of an abnormal metabolism of dopamine in migraine, however, is lacking. METHODS: Plasma and platelet levels of dopamine were measured in patients with migraine with aura or migraine without aura during headache-free periods and in patients with cluster headache during the remission and active periods, as compared with healthy control subjects, using a multichannel electrochemical high-performance liquid chromatography system. RESULTS: Plasma levels of dopamine were not detectable with our methodology. Platelet levels of dopamine were higher in both types of migraine (migraine without aura = .20 +/- .17 ng/10(8) platelets; migraine with aura = .16 +/- .19 ng/10(8) platelets) than in control subjects (.10 +/- .11 ng/10(8) platelets), although in migraine with aura patients the difference was not significant. Patients with cluster headache showed the highest levels of platelet dopamine (.34 +/- .36 ng/10(8) platelets). CONCLUSIONS: Our results support the hypothesis that the dopaminergic system is impaired in migraine and cluster headache and suggest that high platelet levels of dopamine may represent an abnormal biochemical phenotypic trait of these primary headaches.     

Unilaterality of headache in classic migraine

The localization of a headache is a matter of importance for the diagnosis. Migraine is considered to be a unilateral headache. There is, however, only limited information available on the constancy of the unilaterality: how frequently is the pain locked to one side? This aspect is of importance in the differential diagnosis vs. cervicogenic headache, where the pain persistently seems to occur on the one side. In the present study, 31 cases (26F, 5M with a mean age of 40 years; range: 17-63) with a diagnosis of classic migraine were questioned with regard to laterality of headache at the first consultation. A unilaterality as such was present in 42%; unilaterality alternated with bilaterality in 42% of the cases; unilaterality in some form was therefore found in 84% of the cases. In classic migraine, unilaterality thus seems to outweigh bilaterality. In every case of unilaterality there was a sideshift. A side-locked unilaterality thus seems to be a rare phenomenon in classic migraine. These patients were followed-up after between 3 and 9 years; they then filled in a questionnaire (response rate: 81%). The consistency between the two sets of information in the responders was good. Only one case (possibly two) showed a side-locked unilaterality at the time of the questionnaire.     

Kinetics and thermolability of platelet monoamine oxidase in cluster headache and migraine

Platelet monoamine oxidase activity (MAO) from 33 cluster headache patients (17 males, 16 females) and 34 migraine patients (16 males, 18 females) was assayed. The kinetic constants (apparent V_max and apparent K_m) and the thermolability, measured as the ratio of the platelet MAO activity after and before heat treatment (+52°C, 30 min), were determined. The MAO activity and V_max values were significantly lower in cluster headache than in migraine and in both headache disorders compared to a control group (62 males, 66 females). When comparing all groups, K_m was not significantly different except for migraine females, who had lower K_m values compared to control females. Thermolability was significantly higher in cluster headache than in migraine and in both headache disorders compared to the control group. Smokers of five cigarettes or more per day had significantly lower V_max values but similar K_m and thermolability values compared to those smoking less or nothing. The findings of low maximal velocities and high thermolability of platelet MAO in cluster headache and migraine are suggested to represent constitutionally different enzyme properties.     

Platelet aggregation profiles in cluster headache

BACKGROUND: Platelets are activated in patients with cluster headache, during both the remission period and the active cycles. OBJECTIVE: To delineate more clearly the origin of platelet activation in cluster headache. Methods.-Platelet aggregation induced by collagen (0.5 micro g/mL and 2 micro g/mL), adenosine diphosphate (10-5 M and 10-6 M), and platelet-activating factor (10-6 M and 10-7 M) was determined by the Born's method in 26 patients with cluster headache and 24 sex- and age-matched controls. RESULTS: The platelets of patients with cluster headache aggregated significantly less to collagen at a concentration of 0.5 micro g/mL compared to those of controls (P =.04). The extent of platelet aggregation obtained with a higher dose of collagen (2 micro g/mL) was in the same range in both groups. Platelet aggregation obtained via adenosine diphosphate at a concentration of 10-6 M was significantly reduced in patients with cluster headache in comparison to controls (P =.002), but no differences were found at a concentration of 10-5 M. In contrast, the platelets of patients with cluster headache aggregated significantly more to platelet-activating factor at both the concentrations of 10-6 M (P =.001) and 10-7 M (P =.00001) compared to those of controls. CONCLUSIONS: This study suggests that platelet aggregation is impaired in patients with cluster headache during the active phase of the disease. We found hypoaggregation in response to low doses of collagen and adenosine diphosphate, and hyperaggregation when platelets were stimulated with platelet-activating factor. Any interpretation of these results can only be speculative. It may be that impairment of platelet aggregation with collagen and adenosine diphosphate may indicate a derangement of nitric oxide function, while the hypersensitivity to platelet-activating factor may be due to fluctuations in its plasma levels.     

Stress-induced pain and muscle activity in patients with migraine and tension-type headache

We recorded deep pain and surface electromyographic (EMG) responses to stress in 22 migraineurs during headache-free periods, 18 patients with tension-type headache (TTH), and 44 healthy controls. Sixty minutes of cognitive stress was followed by 30 min relaxation. EMG and pain (visual analogue scale) in the trapezius, neck (splenius), temporalis and frontalis areas were recorded. TTH patients had higher pain responses in temporalis and frontalis (with similar trends for trapezius and splenius) and more potentiation of pain during the test than controls. Migraine patients developed more pain in the splenius and temporalis than controls. Muscle pain responses were more regional (more pain in the neck and trapezius compared with the temporalis and frontalis) in migraine than in TTH patients. TTH patients had delayed pain recovery in all muscle regions compared with controls, while migraine patients had delayed pain recovery in a more restricted area (trapezius and temporalis). EMG responses were not different from controls in headache patients, and EMG responses did not correlate with pain responses. TTH patients had delayed EMG recovery in the trapezius compared with controls and migraine patients. These results support the concept that (probably central) sensitization of pain pathways and the motor system is important in TTH. Less pronounced and more regional (either peripheral or central) trigeminocervical sensitization seems to be important in migraine. Surface-detectable muscular activation does not seem to be causal for pain during cognitive stress either in migraine or in TTH.     

Blink reflex in migraine and tension-type headache

The blink reflex was studied in 19 patients with migraine, 10 patients with tension-type headache, and 30 healthy controls. Significantly lower values of R2 and R2' amplitude and size were found in the migraine group, compared with the healthy control group. The differences were independent of the stimulation side (headache or nonheadache) and highly significant (P<0.001). The abnormalities of R2 and R2' amplitude and size were found only during the headache phase of migraine, being normal between migraine attacks. R1 latency and amplitude were normal in all patients. The blink reflex was normal in all the patients with tension-type headache. Subcutaneous injection of sumatriptan in 10 of the 19 migraineurs, during the headache phase, restored R2 and R2' amplitude and size values to normal. Our findings indicate that the brain stem interneuron part of the blink reflex arc may be diffusely suppressed in migraine, only during the headache phase. Furthermore, blink reflex may be an objective laboratory method to monitor the effectiveness of specific drugs proposed for the treatment of migraine.     

Reflux-triggered migraine headache originating from the upper gum/teeth

Two patients with migraine are described who also suffered from gastric reflux. The reflux triggered headaches that originated from the upper gum/teeth and responded to specific reflux treatment.     

5HT in migraine patients with medication-induced headache

Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mmol/1 to mean 6.59 mmol/l ( p < 0.05, Wilcoxon signed rank test), as well as a significant improvement in the number of headache-free days ( p < 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.     

Pain sensitivity and pain reactivity of pericranial muscles in migraine and tension-type headache

We investigated whether experimentally determined, suprathreshold pain sensitivity of pericranial musculature in patients with tension-type headache differs from that of migraine patients or from that of healthy subjects. Furthermore, we looked to see whether differences could be found in the effects of experimental pain induction on EMG activity of pericranial musculature and whether subgroups could be discovered with higher and lower pericranial pain sensitivity within the three diagnostic groups in terms of neurophysiological, psychological and clinical variables. In 20 patients with tension-type headache, 23 patients with migraine without aura, and 29 healthy individuals experimental pain was induced in the temporal muscle by mechanical pressure; pain sensitivity in the entire metrically subdivided suprathreshold pain sensitivity range was measured. Surface EMG activity of pericranial muscles was determined before, during and after experimental pain induction. In addition, headache characteristics as well as personality and mood states were determined and recorded in a standardized fashion. There were no significant differences in pain sensitivity of pericranial musculature between the three groups. Patients with tension-type headache showed significantly higher EMG scores during suprathreshold pain stimulation than did migraine patients. EMG scores of healthy subjects fell between these two groups. With respect to pericranial tenderness significant differences in clinical, neurophysiological and psychological variables were found only between subgroups within the group of patients with tension-type headache. The results indicate that significant differences in the examined groups are found not in pain perception but in the processing or reaction to experimental headache stimuli. In patients with tension-type headache subgroups evolve based on pericranial pain sensitivity with quantitatively and/or qualitatively impaired reactions; for this reason diagnostic grouping according to the IHS classification seems to be pathophysiologically relevant. The intraindividual phasic comparison of pain reactions appears to be more important than the absolute interindividual tonic comparison.     

From migraine to chronic daily headache: the biological basis of headache transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.     

Blink reflex R2 amplitudes in cervicogenic headache, chronic tension-type headache and migraine

Blink reflex R2 amplitude was investigated in seven patients with cervicogenic headache (CEH), 12 patients with chronic tension-type headache, 23 patients with migraine (10 with aura) and 17 headache-free controls. Standard electrical stimulation of the supraorbital nerve was applied and the response was recorded from the ipsilateral and the contralateral orbicularis oculi muscles. Low R2 amplitude was found in CEH patients compared with control subjects. Headache is unilateral in CEH and the ipsilateral and contralateral responses after stimulation on the painful side were most depressed. R2 amplitude was not significantly affected in migraine and tension headache patients. The results suggest that lower brainstem excitability is reduced in CEH. A state of hypoactivity may be present in caudal trigeminal nucleus neurons on the symptomatic side.     

Pain thresholds in daily transformed migraine versus episodic migraine headache patients

OBJECTIVE: The objective of this study was to test whether pain thresholds of patients with episodic migraine (EM) are significantly different from transformed migraine (TM) patients as measured by Quantitative Sensory Testing (QST) and Semmes-Weinstein Monofilaments (SW). BACKGROUND: Although there are many theories, none have undeniably proven why many TM patients are refractory to triptans and other gold standard medications. The hypothesis was that baseline pain thresholds of TM patients are lower than EM patients. METHODS: Episodic (n = 40) and Transformed (n = 41) migraineurs with and without aura were examined with QST and SW over eight locations (bilateral ophthalmic, maxillary, C4/posterior neck, and forearm). All patients completed two visits, baseline and severe migraine. RESULTS: TM patients have lower pain thresholds, than EM patients, as measured on QST and SW testing. A total of 81 out of 129 patients completed both parts of the study at baseline and severe migraine. There were significant differences (P < .05) between EM and TM groups at baseline on maxillary, neck (EM = 45.91 degrees C and TM = 42.94 degrees C), and arm. CONCLUSIONS: TM patients, clinically known to report skin hypersensitivity during migraine, were found to have lower pain thresholds than EM patients, both with severe migraine, and at baseline, measured by QST and SW mechanical testing. As with Burstein's work in EM patients with lowered pain thresholds during their acute migraine, central sensitization may be the explanation for non-responsiveness to triptans in a high proportion of TM patients. The difference in pain threshold at the neck location was such a strikingly frequent difference between EM and TM patients, that this indicates the need for future research to clarify the directional relationship and the relative importance of muscular versus peripheral versus central hypersensitivity in the determination of allodynia.     

Pain-relieving factors in migraine and tension-type headache

We performed the present study to compare patients with migraine and tension-type headache (TTH) in their behaviour during the attacks and the manoeuvres to relieve the pain. One hundred thirty consecutive patients with either migraine (n = 75) or TTH (n = 55) were questioned (including the use of a checklist) concerning their usual behaviour during the attacks and non-pharmacological manoeuvres performed to relieve the pain. The results of the two types of headache were compared. Patients with migraine tended to perform more manoeuvres than patients with TTH (mean: 4.3 vs. 3.6). These manoeuvres included pressing and applying cold stimuli to the painful site, trying to sleep, changing posture, sitting or reclining in bed (using more pillows than usual to lay down), isolating themselves, using symptomatic medication, inducing vomiting, changing diet and becoming immobile during the attacks. The only measure predominantly reported by patients with TTH was scalp massage. Migraineurs, compared to patients with TTH, changing eating habits, pressed the pain site; there were no significant differences between the two groups. The behaviour of patients during headache attacks varies with the diagnosis. Measures that do not always result in pain relief are performed in order to prevent its worsening or to improve associated symptoms. These behavioural differences may be because of the different pathogenesis of the attacks or of various styles of dealing with the pain. They can also aid the differential diagnosis between headaches in doubtful cases.