Plasma Monoamines in Tension-Type Headache

SYNOPSIS
Clinical and pharmacological data suggest a derangement of central monoaminergic systems in tension-type headache. Biochemical evidence has been rarely recognized. These findings may relate with pathophysiological mechanisms of headache or with underlying depression. We measured platelet-rich plasma serotonin and plasma catecholamines (norepinephrine, epinephrine, and dopamine) in 30 patients with tension-type headache and in 20 healthy controls, using High-Pressure Liquid Chromatography. We studied differences between groups and the relation between biochemical parameters and clinical indices evaluating duration and severity of headache and depression. Platelet serotonin levels in tension headache patients were higher than in controls ( P <0.001). Plasma catecholamine levels were lower in patients than in controls ( P 相似文献   

Chronic Tension-Type Headache, Mood Depression and Serotonin: Therapeutic Effects of Fluvoxamine and Mianserine

SYNOPSIS
Forty out-patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society (IHS) Headache Classification Committee. In a controlled trial patients received placebo for a four-week baseline period, then they were randomized in double-blind fashion to therapy with mianserine (30-60 mg/day) or fluvoxamine (50-100 mg/day) for another eight-week period. Frequency of headache, pain severity and analgesic consumption were evaluated using a self-monitoring system. Mood depression was evaluated at 0, 4 and 8 weeks by using Zung'ss Self-Rating Depression Scale and Hamilton Rating Scale for Depression. Both drugs were beneficial in the treatment of chronic tension-type headache. Non-depressed subjects with more severe headache responded best to fluvoxamine, whereas mianserine was more effective in the treatment of depressed patients with moderate headache. These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients.     

文拉法辛与帕罗西汀治疗共患焦虑或抑郁状态的紧张型头痛临床研究

目的:评价文拉法辛与帕罗西汀治疗紧张型头痛共患焦虑或抑郁的疗效及不良反应.方法:将符合ICHD-II诊断标准的35例共患焦虑或抑郁状态的紧张型头痛门诊患者随机分为两组,分别给予文拉法辛(n=18)75mg和帕罗西汀(n=17)20mg,疗程8周.用视觉模拟量表(VAS)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效并观察两组的不良反应.结果:文拉法辛组1例服药后头痛加重停药,帕罗西汀组1例头痛加重停药、1例不能忍受副反应改服其它药物.治疗后2、4、8周两组VAS、HAMD、HAMA评分无统计学意义,但治疗前后以上指标两组均有显著差异.结论:文拉法辛和帕罗西汀在治疗紧张型头痛共患焦虑、抑郁时安全有效,不良反应少.     

Platelet 3H ketanserin binding in tension-type headache

OBJECTIVE: The present study was undertaken to investigate the alterations in platelet 5-HT2 receptor binding in patients with tension-type headache. BACKGROUND: Serotonin (5-HT) has an important but complex role in pain modulation. The involvement of serotonin in tension-type headache has been investigated by studying serotonin in peripheral blood, but results have been inconclusive. There are, however, only a few investigations in which the status of platelet serotonin transporters has been studied by 3H imipramine and 3H paroxetine. The present study was undertaken to investigate alterations in platelet 5-HT2A receptors using 3H ketanserin as a ligand. METHODS: Platelet 3H ketanserin binding was studied in 14 patients with tension-type headache and in 15 healthy controls. The binding characteristics, equilibrium dissociation constant and maximal number of binding sites were determined by Scatchard analysis. RESULTS: There was no change in the equilibrium dissociation constant in the patients with headache as compared to the control group, but subgroup analysis revealed that patients with tension-type headache with a headache index of less than 360 had a significantly lower equilibrium dissociation constant as compared to those with a headache index of more than 360; there was a significant correlation between the equilibrium dissociation constant and the headache index. A significant decrease was observed in the maximal number of binding sites in tension-type headache. No correlation was observed between the maximal number of binding sites and age, duration of illness, or headache intensity. CONCLUSIONS: The findings of the present study show that there is a decrease in the number of binding sites of 5-HT2A receptors in some patients with tension-type headache, suggesting postsynaptic serotonergic dysfunction and the involvement of serotonin in that group.     

Quantitative determination of serum serotonin in the diagnosis of tension headache

A comprehensive psychometric testing and measurement of the serum levels of serotonin by enzyme immunoassay were made before and after treatment with the antidepressant Prodep in 76 patients with chronic tension headache. The patients generally had cephalgia and moderate depression, which were associated with the lower blood concentration of serotonin. A course of antidepressant therapy with Prodep ameliorated headache and depression in the presence of higher serum serotonin levels. Serum serotonin may be regarded as a marker of the severity of pain and depression in patients with chronic tension headache and be an objective indicator of the efficiency of antidepressant therapy.     

Initiating mechanisms of experimentally induced tension-type headache

To elucidate possible myofascial mechanisms of tension-type headache, the effect of 30 min of sustained tooth clenching (10% of maximal EMG-signal) was studied in 58 patients with tension-type headache and in 30 age- and sex-matched controls. Pericranial tenderness, mechanical and thermal pain detection and tolerance thresholds and FMG levels were recorded before and after the clenching procedure. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache free. Mechanical pain thresholds evaluated by pressure algometry remained unchanged in the group which developed headache, whereas thresholds increased in the group which did not develop headache Thermal pain detection and tolerance thresholds remained unchanged in both groups. These findings indicate that, though there may be several different mechanisms of tension-type headache, one of them is sustained muscle contraction. A peripheral mechanism of tension-type headache is therefore possible, whereas a secondary segmental central sensitization seems to be involved in subjects with frequent, tension-type headache. Finally, the increase in pressure pain thresholds in patients who did not develop headache suggested that clenching activated their antinociceptive system, whereas those developing headache were, unable to do so.     

Serotonin metabolism in chronic tension-type headache

Serotonergic neurons play a major role in the regulation of pain and may therefore also be involved in the pathophysiology of tension-type headache. Platelets are important in the regulation of the free serotonin level in plasma and may be a model of serotonergic neurons. The aim of the present study was to investigate the peripheral serotonin (5HT) metabolism in patients with chronic tension-type headache. The 5HT levels in platelets and in plasma, the beta-thromboglobulin (ß-TG) levels in plasma, and the urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) were measured in 40 patients with chronic tension-type headache and in 40 healthy controls. The platelet uptake index was calculated as the ratio between platelet 5HT and plasma 5HT levels. There were, no significant differences in platelet 5HT, plasma 5HT ß-TG, or 5HIAA between patients and controls. The platelet uptake index was significantly lower in patients 243 (136–367) than in controls 352 (202–508), p =0.03. Our results indicate that the peripheral 5HT metabolism is largely normal in patients with chronic tension-type headache.     

The importance of anxiety and depression as factors in chronicization of primary headaches

A multicenter study was carried out in 10 Italian headache centers to investigate the prevalence of anxiety and depression in patients with chronic daily headache(CDH). The study investigated 219 patients (171 F; 48 M) including 53 cases of chronic tension-type headache (CTTH), 99 cases of CTTH+ migraine and 67 cases of transformed migraine (TM). The type of headache diagnosed at the beginning was episodic tension-type headache (ETTH, n=32), ETTH + migraine (n=2), CDH ab initio (n=22), migraine with/without aura (n=151), not classifiable migraine (n=7) and not classifiable headache (n=3). The assessment of anxiety and depression was carried out using a Zung self-rating scale for anxiety (Zung A) and for depression (Zung D). The results show that anxiety and depression levels, in each group, were related to sex (F>M). Anxiety, but not depression, was related to the length of chronicization process. Anxiety and depression did not correlate with type of headache at onset, with ongoing headache or, surprisingly, with the abuse of anti-inflammatory drugs. These data suggest the chronicization is a biological and psychological trait.     

Study of Pressure Pain and Cellular Concentration of Neurotransmitters Related to Nociception in Episodic Tension-Type Headache Patients

The pressure pain threshold of 30 patients affected by tension-type headache was assessed and the values compared with those of a group of 30 age-matched control subjects. In the patient group, pressure pain threshold values were related to the blood cell concentration of some neurotransmitters which are considered to be involved in the genesis and modulation of pain (β-endorphin levels in peripheral blood mono-nuclear cells [PBMCs], substance P and serotonin concentrations in platelets). The pressure pain thrashold was significantly lower in tension-type headache patients than in control subjects (P<0.0006). Significantly lower levels of B-endorphins-in PBMCs and substance P in platelets, as well as significantly higher levels of serotonin in platelets were found in tension, type headache patients compared to the control subjects (P<0.0001). A significant positive correlation was found between pressure pain threshold values and b b-endorphin levels in both control and patient groups (P<0.0001). On the contrary, a statistically significant negative correlation was evident between pressure pain threshold values and substance P levels in platelets in both patients and control subjects (P<0.01 and P<0.001, respectively). In both groups, there was a negative correlation between b b-endorphins in PBMCs and substance P in platelets (patientsP<0.02, controls P<0.001 ).
The findings of altered β-endorphin levels in blood mono-nuclear cells and substance P levels in platelets could be the peripheral biochemical reflection of the low pressure paid threshold values in tension-type headache patients, and support the hypothesis of an impairment of the antinociceptive systems in this form of headache.     

Metabolism and Menstrual Cycle Rhythmicity of Serotonin in Primary Headaches

We investigated the platelet and plasma levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid, in patients suffering from episodic tension-type headache and migraine with and without aura, during headache-free period. In female subjects, blood samples were drawn during the follicular, ovulatory, and late luteal phases of the menstrual cycle. In tension headache and migraine with aura, the group mean values of serotonin and 5-hydroxyindoleacetic acid in platelets and plasma were significantly increased, but migraine without aura patients' levels were normal. The pattern of menstrual cycle-related fluctuations in platelet serotonin levels were similar in female patients with tension headache and in controls, with a maximum value in the follicular phase. In both migraine groups, in contrast, the peak occurred in the ovulatory phase. The results are discussed in view of whether these aberrations in peripheral markers of the metabolism and menstrual cycle-related rhythmicity of serotonin may reflect similar alterations in the central nervous system.     

Are headache and temporomandibular disorders related? A blinded study

To investigate overlaps between headache and temporomandibular disorders (TMD) in a clinical headache population and to describe the prevalence of TMD in headache patients, 99 patients referred to a specialized headache centre were diagnosed according to Research Diagnostic Criteria for TMD (RDC/TMD) and classified in headache groups according to the International Classification of Headache Disorders, second edition for headache diagnoses in a blinded design. The prevalence of TMD in the headache population was 56.1%. Psychosocial dysfunction caused by TMD pain was observed in 40.4%. No significant differences in TMD prevalence were revealed between headache groups, although TMD prevalence tended to be higher in patients with combined migraine and tension-type headache. Moderate to severe depression was experienced by 54.5% of patients. Patients with coexistent TMD had a significantly higher prevalence of depression—most markedly in patients with combined migraine and tension-type headache. Our studies indicate that a high proportion of headache patients have significant disability because of ongoing chronic TMD pain. The trend to a higher prevalence of TMD in patients with combined migraine and tension-type headache suggests that this could be a risk factor for TMD development. A need for screening procedures and treatment strategies concerning depression in headache patients with coexistent TMD is underlined by the overrepresentation of depression in this group. Our findings emphasize the importance of examination of the masticatory system in headache sufferers and underline the necessity of a multidimensional approach in chronic headache patients.     

Leukocyte subsets and cortisol serum levels in patients with migraine without aura and chronic tension-type headache

Leukocyte subsets, serum cortisol and immunoglobulin production were investigated in a group of 12 migraine without aura patients, 12 chronic tension-type headache patients and compared with findings in 12 healthy controls. Chronic tension-type headache patients had statistically significant increased levels of B-lymphocytes (CD19 + cells) ( p < 0.05), while migraine sufferers had a similarly significant decrease in CD8 + T-lymphocytes ( p < 0.05). Migraine patients also had an increased percentage of B-lymphocytes although this failed to reach statistical significance. Immunoglobulin production and cortisol serum levels did not differ in the two headache groups. We conclude that the observed abnormalities in tension-type headache and migraine are unlikely to be a consequence of pain or of hypothalamic-pituitary-adrenal axis dysfunction.     

Serum serotonin in patients with tension headaches

Tension headache (TH) is one of the most frequent types of idiopathic headaches. The leading role in its pathogenesis is played by depression and dysmetabolism of the neurotransmitter serotonin. The subjects were 100 patients with TH. The examination included study of headache intensity, complex psychometric testing, and immune-enzyme measurement of serotonin serum level, performed before and after treatment with the anti-depressant prodep. All the patients had moderate pain syndrome, depression, and moderate or severe anxiety, which demonstrated negative correlation with serotonin serum level. In particular, the intensity of episodic THs (n = 24) was 52 mm visual analogue scale, reactive anxiety level was as high as 51.08 +/- 4.2, the level of depression was moderate (12.9 Beck scale); serotonin blood level showed a tendency to fall (205.72 +/- 6.74 ng/ml). In 76 patients, suffering from chronic THs with a cephalgia intensity of 62 mm visual analogue scale, high indexes of reactive and personal anxiety (46.81 -/+ 2.68 and 54.2 +/- 3.64, respectively), and high depression level were associated with a prominent decrease of serotonin blood concentration (119.38 +/- 9.42 ng/ml). A course of treatment with prodep led to significant decrease of headache intensity and improved depression, while an increase of serum serotonin level was observed. Thus, serotonin serum level may be used as a marker of pain intensity and the level of depression, and an objective indicator of anti-depressive therapy.     

Behavioral and psychologic aspects of the pathophysiology and management of tension-type headache

Behavioral and psychologic factors in tension-type headache are reviewed with reference to pathophysiology, comorbid psychiatric disorders, headache triggers, and behavioral treatment, including the efficacy of behavioral treatments, brief minimal contact administration of behavioral treatment, therapeutic mechanisms underlying the effectiveness of behavioral treatments, and the integration of drug and behavioral treatments. Anxiety or depression may contribute to central sensitization that underlies frequent tension-type headaches. Excessive analgesic use, comorbid psychiatric disorders, or persistent unaddressed headache triggers may limit the effectiveness of headache treatment. Available drug and behavioral treatments are effective for episodic tension-type headache, but are only moderately effective for chronic tension-type headaches. The combination of behavioral and preventive drug therapies may improve outcomes for patients with chronic tension-type headache.     

The wavelength of light causing photophobia in migraine and tension-type headache between attacks

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia is an abnormal perceptual sensitivity to light experienced by most patients with headache during and, also, between attacks. METHODS: We examined the discomfort threshold to light of low, medium, and high wavelengths in a group of patients with migraine (n=21), patients with tension-type headache (n=19), and healthy controls (n=21). RESULTS: The results indicate that the migraine group had significantly lower discomfort thresholds at the low (P=.001) and high (P=.031) wavelengths compared with both the tension-type headache and control groups; the latter two groups had similar average discomfort levels at these two wavelengths. With the medium wavelength, the control group had significantly higher discomfort thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; the latter two groups had similar discomfort levels at this wavelength. With unfiltered (white) light, the migraine group had the lowest discomfort threshold and the control group the highest (P=.026), whereas the tension-type headache group had an intermediate discomfort threshold. CONCLUSIONS: There were significant differences between migraineurs, patients with tension-type headache, and healthy controls in the wavelengths that are uncomfortable between attacks.     

Improvement of tension-type headache when treating wrinkles with botulinum toxin A injections

Botulinum toxin A has been used to treat a spectrum of neuromuscular diseases. In recent years, it has become an accepted treatment for dynamic facial wrinkles. Following treatment of glabella and forehead wrinkles with botulinum toxin A, 9 of 134 patients coincidentally reported improvement of tension-type headache. We have retrospectively studied this group of patients in whom improvement of facial wrinkles closely paralleled improvement of tension-type headache. This observation suggests a role for muscle action in tension-type headache and a novel treatment.     

Muscular Factors are of Importance in Tension-Type Headache

Recent studies have indicated that muscular disorders may be of importance for the development of increased pain sensitivity in patients with chronic tension-type headache. The objective of the present study was to investigate this hypothesis by examining the pain perception in tension-type headache with and without muscular disorders defined as increased tenderness. We examined 28 patients with episodic tension-type headache, 28 patients with chronic tension-type headache, and 30 healthy controls. Pericranial myofascial tenderness was recorded with manual palpation, and pressure pain detection and tolerances in cephalic and extracephalic locations with an electronic pressure algometer. In addition, thermal pain sensitivity and electromyographic activity were recorded. The main result was significantly lower pressure pain detection thresholds and tolerances in all the examined locations in patients with chronic tension-type headache with a muscular disorder compared to those without a muscular disorder. There were no such differences in any of the examined locations when the two subgroups of patients with episodic tension-type headache were compared. Thermal pain sensitivity did not differ between patients with and without a muscular disorder, while electromyographic activity levels were significantly higher in patients with chronic tension-type headache with than in those without a muscular disorder. Our results strongly indicate that prolonged nociceptive stimuli from the pericranial myofascial tissue sensitize the central nervous system and, thereby, lead to an increased general pain sensitivity. Muscular factors may, therefore, be of major importance for the conversion of episodic into chronic tension-type headache. The present study complements the understanding of the important interactions between peripheral and central factors in tension-type headache and may lead to a better prevention and treatment of the most prevalent type of headache.     

Tension-type headache

Tension-type headaches, the most prevalent form of headache, are differentiated as being either episodic or chronic. The episodic form is a physiologic response to stress, anxiety, depression, emotional conflicts, fatigue, or repressed hostility. Treatment focuses on the use of over-the-counter or prescribed simple analgesics for pain relief. Successful treatment of the chronic form depends on recognition of depression or persistent anxiety states. Primary care physicians can effectively manage most of these patients with nonhabituating anxiolytic or antidepressant medications; however, referrals for psychotherapy may be required in some cases. When tension-type headaches occur in children and adolescents, the physician must explore the patient's family and social relationships as well as school performance. In addition to nonhabituating drug therapies, family counseling and biofeedback may be helpful. In coexisting migraine and tension-type headaches, nonhabituating analgesics may be used for the relief of acute pain; the use of ergotamine and triptans should be restricted to relief of the hard or sick headache. Tricyclic antidepressants or monoamine oxidase inhibitors are the gold standards for prophylaxis, although the selective serotonin reuptake inhibitors may be indicated in less severe cases. Several forms of biofeedback have also proved effective. Nonetheless, some patients with this form of headache may require psychiatric treatment for severe depression.     

Tension-type headache

Tension-type headaches, the most prevalent form of headache, are differentiated as being either episodic or chronic. The episodic form is a physiologic response to stress, anxiety, depression, emotional conflicts, fatigue, or repressed hostility. Treatment focuses on the use of over-the-counter or prescribed simple analgesics for pain relief. Successful treatment of the chronic form depends on recognition of depression or persistent anxiety states. Primary care physicians can effectively manage most of these patients with nonhabituating anxiolytic or antidepressant medications; however, referrals for psychotherapy may be required in some cases. When tension-type headaches occur in children and adolescents, the physician must explore the patient's family and social relationships as well as school performance. In addition to nonhabituating drug therapies, family counseling and biofeedback may be helpful. In coexisting migraine and tension-type headaches, nonhabituating analgesics may be used for the relief of acute pain; the use of ergotamine and triptans should be restricted to relief of the hard or sick headache. Tricyclic antidepressants or monoamine oxidase inhibitors are the gold standards for prophylaxis, although the selective serotonin reuptake inhibitors may be indicated in less severe cases. Several forms of biofeedback have also proved effective. Nonetheless, some patients with this form of headache may require psychiatric treatment for severe depression.     

Increased platelet serotonin content and hypersecretion from dense and a-granules in vitro in tension-type headache

We investigated platelet aggregation and secretion from dense and a-granules in vitro in 28 tension-type headache (TH) patients and 26 healthy controls. We also measured basal platelet serotonin levels, Platelet aggregation was normal in TH, but the secretion of serotonin and platelet factor 4 (PF4) was significantly increased in response to 0.5 and 2.0 mg/ml collagen and to 1.0 mmol/l PAF. The basal platelet serotonin levels were also higher in patients than in controls. The mechanisms of platelet hypersecretion remain to be determined, but the increased secretion of serotonin is probably in part related to the increased basal levels. The increased platelet serotonin in TH patients may reflect an enhanced serotonin turnover.