Buspirone vs amitriptyline in the treatment of chronic tension-type headache

Objectives - The aim of this study was to explore the efficacy of buspirone (BSR), in comparison with amitriptyline (AML) in the prophylactic treatment of chronic tension-type headache (CTH), in an open and randomized clinical trial. Material and methods - Twenty-six CTH patients (10 men and 16 women) were treated with BSR (30 mg daily) for 12 weeks. A parallel group of 32 CTH patients (12 men and 20 women) was treated with AML (50 mg daily). The major clinical parameters evaluated were the headache index (days with headache per month), the frequency of drug use for the acute management of headaches, the patients' opinion for the treatment and the Hamilton anxiety and depression rating scales. Results - During the study 9 patients dropped out (4 from the BSR group and 5 from the AML group). Twelve (54.5%) patients from the BSR group responded to treatment (&50% reduction in the headache index), compared to 17 (60.7%) from the AML group. In the BSR group, 14 (53.8%) patients reported various mild side effects (nausea most frequently), vs 21 (65.6%) of the AML group (mouth dryness more frequently). Patients treated with AML had better opinion and used less drugs for the acute treatment of headaches than the BSR treated patients. Conclusion - These results suggest that BSR may be effective in the prophylactic treatment of CTH, and that further investigation in a placebo controlled study, is needed.     

Sumatriptan has no clinically relevant effect in the treatment of episodic tension-type headache

In a randomized, multi-centre, double-blind, placebo-controlled, parallel group study, the efficacy of 100 mg oral sumatriptan was compared with that of placebo in the treatment of episodic tension-type headache. The patients were recruited from the general population in the vicinity of the study centres, by randomly mailed invitations. One or more attacks were treated with sumatriptan by 54 patients and with placebo by 57 patients. A seven-point verbal rating scale was used for hourly assessments of headache relief, 1–4 h after treatment According to the predefined primary end-point of the study, which was moderate or complete relief of headache 2 and 4 h after treatment of the first attack, there was no significant difference between sumatriptan and placebo treatment Sumatriptan did perform statistically significantly better than placebo at some time points, but the effect was not considered clinically relevant We conclude that sumatriptan should not be used in treatment of tension-type headache. The marked difference in effect of sumatriptan in treatment of migraine and tension-type headache argues against the idea that migraine and tension-type headache are part of a continuum of headache disorders.     

Blink reflexes in chronic tension-type headache patients and healthy controls

ObjectiveTo use the R2 component of nociceptive-specific blink reflex (nBR) to probe the trigeminal nociceptive system and compare chronic tension-type headache (CTTH) patients and healthy controls.MethodsThirty patients with CTTH and 30 age- and sex-matched healthy control subjects were included. nBR were evoked by painful electrical pulses (0.5 ms duration), delivered by a concentric electrode placed on the left lower forehead close to the supraorbital foramen. The EMG activity in the orbicularis oculi muscles was recorded bilaterally. The electrical stimulus intensities to evoke individual sensory threshold (Is) and pin-prick pain sensation (Ip) were assessed. A fixed stimulation intensity of 1.5× Ip was used to evoke the nBR. The perceived pain intensity of the electrical stimulus (I_BR) was assessed by the subjects on a 0–10 cm visual analogue scale (VAS).ResultsIs did not differ between CTTH patients and controls (P = 0.687) but were lower in females than in males (P = 0.020). CTTH patients had higher scores on I_BR than controls (P = 0.026). ANOVA showed significantly higher pre-stimulus EMG values in CTTH patients on the left (stimulated) side (P < 0.001), whereas there were no differences between males and females (P > 0.168). There were no significant differences in the absolute values of the nBR, however CTTH patients had significantly lower values of the normalized root mean square (RMS) (P = 0.035) and area under the curve (AUC) (P = 0.042) of the nBR on the left side compared with control subjects with no sex-related differences (P > 0.070). The onset latencies and duration were not significantly different between CTTH and control subjects or between female and male subjects (P > 0.270). There was no significant correlation between any of the BR parameters (RMS, AUC) and clinical characteristics of CTTH (headache intensity and duration) (P > 0.163).ConclusionsThe results of the present study did not detect a significantly different blink reflex response in CTTH patients, but suggested that painful electrical stimulation was associated with consistent increases in eye muscle activity on the same side.SignificanceThese findings add further information to central nociceptive pathways in CTTH patients.     

The trigemino-cervical reflex in tension-type headache

To investigate the pathophysiology of tension-type headache (TTH) with special reference to central mechanisms and to the involvement of the trigeminal system. Short latency responses can be recorded in tonically active sternocleidomastoid muscle after stimulation of the infraorbital branch of the trigeminal nerve (the trigemino-cervical reflex). This brainstem reflex was studied in 15 healthy subjects, in 15 patients with episodic tension-type headache (ETTH) and in 15 patients with chronic tension-type headache (CTTH) outside of the pain attacks. The trigemino-cervical response was abnormal, in the size or latency, in 13 patients with CTTH and in only one patient with ETTH. This finding strongly suggests that only in the CTTH the underlying pathophysiology involves the trigeminal system. The trigemino-cervical reflex is a sensitive method to evaluate the involvement of the trigeminal brainstem neurones in TTH and their assessment may provide useful diagnostic and prognostic information.     

Effects of induced stress on experimental pain sensitivity in chronic tension-type headache sufferers

Background and purpose:  It has been proposed that stress may contribute to chronic tension-type headache (CTH) through hyperalgesic effects on already sensitized pain pathways in CTH sufferers. This hypothesis could be partially tested by examining effects of stress on mechanical and thermal pain sensitivity in CTH sufferers. Such examinations have not been reported to date.
Materials and methods:  In the present study, we measured cephalic and extra-cephalic pressure [pressure-pain threshold (PPT)] and cold-pain thresholds (CPT) in CTH sufferers ( n  = 8 females, n  = 8 males) and healthy control subjects ( n  = 8 males, n  = 7 females) recruited from the general population before and after exposure to a 15-min stressful mental task.
Results:  Results indicated that PPT's at head and hand were lower in the CTH compared with control group both before and after task exposure. PPT's and CPT's decreased from pre- to post-task in both groups, with a significantly greater pre- to post-task reduction in cephalic PPT in the CTH compared with control group. Subjective stress increased from pre- to post-task in both groups and did not differ between groups. In the CTH group, stress reactivity was negatively correlated with PPT's, whilst absolute stress levels were positively correlated with pre- to post-task decrease in PPT's.
Conclusions:  The main finding is an enhanced hyperalgesic effect of stress on cephalic pressure-pain sensitivity in the CTH sufferers compared with the healthy controls. The results support the hypothesis that stress may contribute to CTH through hyperalgesic effects on already sensitized pain pathways in CTH sufferers.     

Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache

It has been proposed that nitric oxide (NO) induced headache in primary headaches may be associated with release of calcitonin gene-related peptide (CGRP). In the present study we aimed to investigate plasma levels of CGRP during headache induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min on two headache-free days. Blood samples were collected at baseline, 10, 20 and 60 min after start of infusion. Both patients and controls developed significantly stronger immediate headache on the GTN day than on the placebo day and the headache was significantly more pronounced in patients than in controls. There was no difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN day did not differ between patients and controls (P=0.36). Both in patients and controls, CGRP levels changed significantly over time, on both the GTN and placebo days (P < 0.05). The present study indicates that NO-induced immediate headache is not associated with release of CGRP.     

Prophylactic treatment of chronic tension-type headache using botulinum toxin type A

Chronic tension-type headache is a common condition, the pathophysiology of which is not well understood. Over-activity of the pericranial muscles is thought to play a role, although sustained muscle contraction is probably a consequence, rather than a cause, of headache. Botulinum toxin type A (BTX-A) is useful in many conditions involving excessive muscle contraction and may therefore be effective in relieving the pain associated with this type of headache. To investigate the efficacy of BTX-A in relieving pain associated with chronic tension-type headache, a double-btind, randomised, placebo-controlled study was carried out, in which 37 patients received BTX-A, injected into the temporalis or cervical muscles of the neck. Clinical outcome was measured over a 4-month study period using headache diaries and chronic pain index scores. Patients treated with BTX-A showed an improvement in headache severity over the 4-month study period, with 13 out of 22 patients showing a 25, 50 or >50% improvement in headache score at Month 3 compared with two out of 15 patients in the placebo group. The number of headache-free days increased significantly in the BTX-A-treated patient group, and patients recorded an improvement in quality of life following BTX-A injection. It can be concluded that intramuscular injection of BTX-A is an effective treatment for chronic tension-type headache.     

女性紧张性头痛及经期偏头痛影响因素的比较

目的比较女性紧张性头痛(TTH)及经期偏头痛(MM)的影响因素。方法收集104例女性TTH患者(TTH组)及91例MM患者(MM组)的临床资料。采用视觉模拟评分法(VAS)和头痛影响测评量表-6(HIT-6)对其头痛程度、生活质量进行评估,并采用汉密尔顿焦虑(HAMA)、抑郁量表(HAMD)对患者情绪障碍进行测定。结果 TTH组与经期相关19例,累积发病率18.3%;MM组与经期相关59例,累积发病率64.8%。与TTH组比较,MM组发病年龄显著降低,病程、家族史,焦虑、抑郁、重度疼痛、HIT-6(Ⅳ级)、共病的比率,以及HAMA、HAMD评分均显著升高(P0.05~0.01),而文化程度、吸烟、饮酒、职业差异无统计学意义(均P0.05)。无先兆的月经相关性偏头痛(MRM)、无先兆的单纯月经性偏头痛(PMM)及非月经性无先兆偏头痛患者发病年龄、家族史、VAS及HIT-6评分差异有统计学意义(P0.05~0.01)。结论与女性TTH比较,MM发病年龄更轻、病程更长,也更易合并焦虑、抑郁。在不同类型MM中,PMM发病年龄更早,有家族史的比率更高;而MRM的重度疼痛率及HIT-6评分最高。     

Monocyte chemotactic and phagocytic responses in migraine and tension-type headache patients

Monocyte chemotactic and phagocytic responses were assessed in two groups of migraine patients (with and without aura) and in two groups of tensiontype headache patients (episodic and chronic). The chemotactic but not the phagocytic response, assessed interictally, is significantly lower in migraine patients (p<0.006) and in episodic tension-type headache patients, though not so significantly in the latter (p<0.05), than in the control individuals. The chemotactic response tends to increase significantly during attack in migraine patients both with and without aura (p<0.008 and p<0.007 respectively). The same was evident for the phagocytic response in both migraine patient groups (p<0.007 and 0.0004). No modifications of monocyte functions were found during attacks neither in episodic nor chronic tension-type headache patients. These findings suggest that one or more mediators of neurogenic inflammation having phagocytic and chemotactic enhancing properties (substance P, prostaglandin E and thromboxane A2 etc.) are implicated in the modification of monocyte function. The demonstration of a defect in monocyte function during the interictal period in migraine patients confirms the results of recent research which evidenced reduced capacity of monocyte to phagocyte and kill microorganisms in the course of migraine. Paper presented at the National Congress at Sorrento in 1991 and selected by the Editorial Board of the Journal     

Evidence for an altered dopamine-hydroxylase activity in migraine and tension-type headache

Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.     

Botulinum toxin type A injections for myofascial pain syndrome and tension-type headache

Myofascial pain syndrome (MPS) is characterised by acute and specific pain affecting the piriformis, iliopsoas or scalenus anterior muscles. Tension-type headache (TH) is a common pathological condition, which can be chronic or episodic. Based on its muscle-relaxant properties, botulinum toxin type A (BTX-A) has demonstrated efficacy in a variety of conditions involving dysregulated muscle contractions. Patients with MPS ( n = 40) or TH (n = 20) were recruited to two randomised, single-blind studies, respectively. Each patient received either BTX-A or methylprednisolone, injected into the affected muscles after administration of a local anaesthetic. Pain was assessed at baseline, and 30 and 60 days post-treatment using a standard visual analogue scale. At 30 days post-injection, the mean pain score in all treatment groups was reduced compared with baseline in both studies, although the difference between treatment groups was not significant at this time in either study. However, by 60 days post-injection, the mean pain score has continued to fall in the BTX-A treatment groups, compared with a waning of the steroid therapeutic activity in the controls. The net effect was a highly significant difference between the two treatments in both the MPS ( P < 0.0001) and TH ( P < 0.0005) studies. No major adverse events were reported. In conclusion, BTX-A produces a more prolonged pain relief than methylprednisolone in patients suffering from MPS or TH.     

Effect of serotonergic antidepressant therapy on temperament and character scales in patients with chronic tension-type headache

The purpose of the present study was to assess a group of patients with chronic tension-type headache (CTTH) and control subjects using the personality questionnaire proposed by Cloninger and to determine possible changes in the Temperament and Character Inventory (TCI) patterns of CTTH patients after therapy with serotonergic antidepressants. Forty-five patients with CTTH filled out the TCI and Beck Depression Inventory (BDI) before and after 4-month prophylactic therapy with serotonergic antidepressants. A total of 50 age-, sex- and education level-matched healthy subjects were selected as a control group. During the pretreatment period patients were found to have higher harm avoidance and lower self-directedness scores than healthy comparison subjects. During the post-treatment period, although harm avoidance scores decreased and self-directedness scores increased, harm avoidance scores were still significantly higher and self-directedness scores significantly lower in CTTH patients than in controls. After using BDI score and age as covariates at the post-treatment period, harm avoidance scores were still higher in patients with CTTH while self-directedness scores did not differ between CTTH patients and controls. These findings suggest state and trait dependence of harm avoidance, and strong state dependence of self-directedness scores in CTTH patients. When interpreting data regarding personality measured by the TCI in CTTH patients, the effects of depressive symptomatology should be taken into account.     

Magnesium as a treatment for paediatric tension-type headache: a clinical replication series

Abstract The objective was to determine the initial utility of magnesium salt as a treatment for paediatric episodic and chronic tension-type headache (TTH). The study took the form of a clinical replication series in the Outpatient Headache Center at the National Neurological Institute C. Besta, Milan, Italy. The patients were five children/adolescents with episodic and four with chronic TTH reporting consecutively for treatment. Magnesium pidolate (2.25 g) was given twice per day for two months, with one year of follow-up. No other treatment was provided. Patients with episodic TTH revealed 76.0% symptom reduction, with 80% of the sample achieving reductions greater than 50%. The patients with chronic TTH revealed 87.5% symptom reduction, with 100% of the sample achieving reductions greater than 50%. Analgesic consumption decreased significantly for chronic TTH. Only one child took medication in the episodic TTH group. No significant changes occurred with respect to depression and anxiety, but these measures were not clinically elevated at the start of treatment. Although uncontrolled, the initial findings are encouraging and suggest that further, better controlled research is warranted.     

Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache

Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P < 0.02) and in skin overlying the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ between groups in anterior tibial muscle and skin. Quantitative sensory testing revealed increased pain sensitivity in patients as assessed by pressure-controlled manual palpation (local tenderness score, LTS; P < 0.01) and by pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the trapezius muscle, but not the anterior tibial muscle. In summary, this study demonstrates lower pain thresholds in muscle and skin of the cephalic region but not in lower limb muscle and skin in patients with chronic tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.     

Pharmacological and behavioral treatment of pediatric migraine and tension-type headache

The problem concerning the treatment of pediatric headache has been the object of several recent reports. Some of the same medications used to treat adult headache problems are also utilized with children but usually at smaller dosages and in different combinations. The recent application of behavioral approaches, in particular biofeedback, for treatment of children’s headaches has been an effective alternative to drugs without the problematic and dangerous side effects of pharmacological treatments. The purpose of this review is to give some indications about the most common pharmacological therapies for migraine and tension-type headache in children, and also to discuss the use of behavioral therapies, in particular biofeedback, as excellent alternatives to drugs.     

A comparative analysis of personality profile and muscle tenderness between chronic migraine and chronic tension-type headache

Abstract This study was aimed at comparing the personality profile, the psychiatric comorbidity (depression and anxiety) and the tenderness of the pericranial and cervical muscles in women with chronic migraine (CM) and chronic tension-type headache (CTTH). Forty-one CM and 34 CTTH women were enrolled. A clinical evaluation (according to SCID-I) and a psychometric assessment (MMPI-2, STAI-1 and STAI-2) were performed. After palpation, a Pericranial muscle Tenderness Score (PTS) and a Cervical Muscle Tenderness Score (CTS) were calculated. No significant difference was detected in MMPI-2, STAI-1, STAI-2, PTS and CTS scores between the two groups. Anxiety and depression were present in 80% of CM and in 63% of CTTH women. We did not find any significant difference either in the personality profile or in the muscle tenderness between CM and CTTH patients. This similarity points to a role of these factors, in association with psychiatric comorbidity, in the chronicisation of headache.     

Remission of mood disorder with psychotic features after treatment with mirtazapine

The antidepressant mirtazapine enhances both noradrenergic and serotonergic transmission by blocking α_2-adrenergic presynaptic auto- and heteroreceptors, respectively. We here report on three patients with mood disorders with psychotic features (two cases with depressive and one with bipolar disorder). Treatment with mirtazapine significantly improved not only their depression, but also their delusions. Depressive symptoms were only partially responsive and delusions unresponsive in all three patients to previous antidepressive and/or antipsychotic treatment, and only mirtazapine induced persistent improvement. These clinical cases suggest that mirtazapine can be a valid alternative for patients with depression with psychotic features and partial treatment-resistance.     

偏头痛和慢性紧张型头痛血浆精氨酸加压素、催产素及环核着酸含量测定

用放射免疫分析法测定了２８例偏头痛、１０例慢性紧张型头痛患者和１６例健康对照组血浆精氨酸加压素（ＡＶＰ）、催产素（ＯＴ）、环磷酸腺苷（ｃＡＭＰ）及环磷酸鸟苷（ｃＧＭＰ）含量。结果表明，偏头痛发作期ＡＶＰ含量下降、ｃＡＭＰ含量升高，偏头痛间歇期ｃＧＭＰ含量下降，血浆ＯＴ含量在发作期和间歇期均明显下降。慢性紧张型头痛患者血浆ＡＶＰ、ＯＴ、ｃＡＭＰ和ｃＧＭＰ与对照组比较均无显著性差异。结果提示，血浆ＡＶＰ和ＯＴ水平降低以及环核苷酸的代谢异常与偏头痛发病机制有关。     

Pericranial injection of botulinum toxin type A (Dysport®) for tension-type headache – A multicentre, double-blind, randomized, placebo-controlled study

Increasingly, botulinum type A toxin is used to influence pathologically increased muscle activity in conditions such as dystonia and spasticity. Studies have also assessed its efficacy in tension-type headache, where muscle tenderness may be increased. We undertook a prospective, multicentre, randomized, double-blind, placebo-controlled trial. Patients received injections of Dysport^® (total dose of 420 or 210 units) or saline placebo in 18 sites on the head and neck. Of 125 patients treated, 118 were included in the intention-to-treat dataset. No significant differences between each verum group and placebo were seen for the primary efficacy parameter – change in the number of headache-free days at 4–8 weeks after injection compared with 4 weeks before injection. The groups receiving 420 or 210 units of Dysport experienced 2.60 and 2.87 more headache-free days respectively, compared with 1.93 more headache-free days for the placebo group ( P  = 0.66 versus 420 units; P  = 0.52 versus 210 units). Treatment with 420 units of Dysport was associated with significant improvements compared with placebo for two secondary efficacy parameters: mean change in headache duration from baseline to weeks 8–12 ( P  < 0.05) and improved global physician and patient assessment scores ( P  < 0.05). Further studies should address the possible value of multiple injections with extended observation periods, dose optimization, and whether duration of headache history and number of previous treatments are predictors of patient response.     

三叉神经-颈反射在无先兆偏头痛和慢性紧张型头痛中的意义

目的 研究三叉神经-颈反射(trigemino-cervical reflex,TCR)在无先兆偏头痛(migraine without aura,MWOA)和慢性紧张型头痛(chronic tension-type headache,CTTH)中的意义.方法 选取2009年1月至2010年2月福建省级机关医院门诊25例单侧MWOA患者、25例CTTH患者及36名健康成年对照进行TCR检测.刺激一侧眶下神经(infraorbital nerve,ION),可在同侧胸锁乳突肌(sternocleidomastoid muscle,SCM)上记录到一个短潜伏期正-负波,即TCR.比较各组TCR参数[峰潜伏期(PL)、刺激前后波幅比率的平方根(A值)]的差异.结果 MWOA组和CTTH组双侧PLP19[MWOA右侧(19.81±1.79)ms,左侧(19.49±1.95)ms;CTTH右侧(19.16±1.67)ms,左侧(19.56±2.02)ms]、PLN31[MWOA右侧(30.75±2.35)ms,左侧(30.44±3.75)ms;CTTH右侧(30.32±3.47)ms,左侧(30.11±3.34)ms]较对照组缩短(t=2.027～3.654,P＜0.05);CTTH组和MWOA组双侧PLP19、PLN31及A值差异无统计学意义.结论 MWOA组和CTTH组的双侧PLP19、PLN31潜伏期较对照组缩短,提示三叉神经、脑干系统参与MWOA、CTTH的发病机制;但两组病例无明显差异,MWOA和CTTH在内源性疼痛调节系统的某个部位如三叉神经或脑干系统,存在共同的功能障碍.