Salivary inflammatory markers in tension type headache and migraine: the SalHead cohort study.

OBJECTIVE: To investigate the possible association between salivary CRP, IL-1ß, and IL-6 levels, depression/anxiety and migraine, and tension type headache (TTH) in saliva of these patients. METHOD: A longitudinal prospective study was conducted on 30 migraineurs, 30 TTH patients, and 30 age-matched healthy controls. Anxiety and depression were measured by using the Hamilton Anxiety Rating Scale (HAM-A), and the Beck Depression Inventory (BDI). Salivary IL-6, IL-1ß, and CRP were collected in distinct time points as A: headache-free period, B: during headache, C: 1 day after headache attack, and measured by using ELISA kits. RESULTS: No significant differences were found in time variation of CRP, IL-1ß, and IL-6 levels between migraine and TTH (p > 0.05). IL1-ß had the highest discriminative value (area under the curve = 0.924, p value < 0.001), and then CRP (area under the curve = 0.763, p value < 0.001) and IL-6 (area under the curve = 0.537, p value = 0.58). CRP and IL-6 were negatively correlated with HAM-A and BDI scores. CONCLUSION: IL1-ß had the highest discriminative value between headache patients and controls compared with CRP and IL-6. CRP and IL-6 were correlated with lower symptom scores of anxiety and depression prior or immediately after the headache period in patients groups.

Cognitive Performance and the Alteration of Neuroendocrine Hormones in Chronic Tension-Type Headache.

Tension-type headache (TTH) is the most prevalent primary headache. Chronic TTH (CTTH), the most serious form of TTH, is refractory, with a high socio-economic burden. Research studies have shown patients with migraine often had cognitive impairment, but few studies have focused on the cognition in patients with CTTH. In this study, we assumed that patients with CTTH also have cognitive impairments, which are modulated by the neuroendocrine state. Participants were recruited, including patients with CTTH and healthy controls. Cognitive ability was evaluated using the Montreal Cognitive Assessment and the Nine Box Maze Test. The administration of neuroendocrine hormones has been established to be associated with cognitive performance, and we detected the hormonal changes in the hypothalamus-pituitary-adrenal axis, the hypothalamus-pituitary-thyroid axis, and gonadotropin-releasing hormone. These results showed that compared to the controls, significant cognitive impairment and neuroendocrine dysfunction were present in the patients with CTTH. We also assessed the correlations between the neuroendocrine hormones and Pittsburgh Sleep Quality Index score, 17-term Hamilton's Depression Scale score, pain intensity, and duration of pain to determine whether the neuroendocrine hormones had any associations with these symptoms of CTTH. These results showed that changes in neuroendocrine hormones were involved in these symptoms of CTTH. Intervention with the neuroendocrine state may be a strategy for CTTH treatment.

CGRP in human models of primary headaches.

Objective To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. Discussion Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown. Conclusion Human models of primary headaches have elucidated the role of CGRP in headache pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used to predict efficacy of CGRP antagonists in migraine patients.

Asociación de la frecuencia y duración, pero no la intensidad, de la cefalea con la hipersensibilidad mecánica y la salud en pacientes con cefalea de tensión / Association between the frequency and duration, but not the intensity, of headache with mechanical hypersensitivity and the health of patients with tension-type headache

Introducción. La asociación entre las variables clínicas de la cefalea y otras variables neurofisiológicas o de salud es controvertida. Objetivo. Determinar la asociación de la frecuencia, duración e intensidad del dolor con la sensibilidad mecánica craneocervical, considerando el efecto de otras variables de salud y físicas. Pacientes y métodos. Se incluyeron 72 pacientes con cefalea de tensión. Se mantuvo un diario mensual para determinar la frecuencia, duración e intensidad del dolor. Se calcularon los umbrales de dolor a la presión (UDP) y la sensibilidad a la palpación sobre la región craneocervical, calidad de vida (Short Form-36), discapacidad, depresión y movilidad cervical. Se introdujeron todas las variables en modelos de regresión logística jerárquica para determinar las interacciones. Resultados. Se encontraron correlaciones entre la frecuencia y duración de la cefalea, pero no la intensidad, con el resto de variables. El análisis de regresión mostró que la combinación del UDP sobre el temporal, dolor corporal, edad y rol físico explicaba el 22,3% de la varianza de la frecuencia, mientras que la combinación de salud general, UDP sobre el trapecio superior y frecuencia del dolor explicaba el 20% de la varianza de la duración (p < 0,001). Conclusiones. Este estudio ha encontrado que la frecuencia y la duración de la cefalea, pero no la intensidad, se encuentran asociadas con variables neurofisiológicas, como el UDP sobre el cuello/cabeza o la percepción de dolor generalizado en la cefalea tensional. Otras variables, como la edad, el rol físico y la salud general también mostraron una asociación con la frecuencia y la duración de la cefalea (AU)

Introduction. The association between headache clinical parameters and other health-related and neuro-physiological outcomes is controversial. Aim. To investigate the association between headache frequency, duration and intensity with cranio-cervical pressure sensitivity considering the interaction of health-related and physical outcomes. Patients and methods. Seventy-two individuals with tension type headache were included. A 1-month diary was used to assess headache frequency, duration and intensity. Pressure pain thresholds (PPT) and peri-cranial tenderness to palpation, health-related quality of life (Short Form-36), disability, depression, and cervical range of motion were the outcomes. All outcomes were introduced into hierarchic logistic regression models to assess potential associations. Results. Several associations between headache frequency and duration, but not intensity, with the remaining variables were found. Regression analysis showed that PPT over the temporalis muscle, bodily pain, age and physical role explained the 22.3% of the headache frequency, whereas general health, PPT over the upper trapezius and headache frequency explained 20% of headache duration (p < 0.001). Conclusions: This study found that headache frequency and duration, but not headache intensity, were associated with neurophysiological outcomes, e.g., cranio-cervical pressure sensitivity, and bodily pain in tension type headache. Other variables including age, physical role and general health were also associated with headache frequency and duration (AU)

Does exercise make migraines worse and tension type headaches better?

Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

Effect of the emotional freedom technique on perceived stress, quality of life, and cortisol salivary levels in tension-type headache sufferers: a randomized controlled trial.

OBJECTIVE: To evaluate the short-term effects of the emotional freedom technique (EFT) on tension-type headache (TTH) sufferers. DESIGN: We used a parallel-group design, with participants randomly assigned to the emotional freedom intervention (n = 19) or a control arm (standard care n = 16). SETTING: The study was conducted at the outpatient Headache Clinic at the Korgialenio Benakio Hospital of Athens. PARTICIPANTS: Thirty-five patients meeting criteria for frequent TTH according to International Headache Society guidelines were enrolled. INTERVENTION: Participants were instructed to use the EFT method twice a day for two months. OUTCOME MEASURES: Study measures included the Perceived Stress Scale, the Multidimensional Health Locus of Control Scale, and the Short-Form questionnaire-36. Salivary cortisol levels and the frequency and intensity of headache episodes were also assessed. RESULTS: Within the treatment arm, perceived stress, scores for all Short-Form questionnaire-36 subscales, and the frequency and intensity of the headache episodes were all significantly reduced. No differences in cortisol levels were found in any group before and after the intervention. CONCLUSIONS: EFT was reported to benefit patients with TTH. This randomized controlled trial shows promising results for not only the frequency and severity of headaches but also other lifestyle parameters.

Plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in patients with tension-type headache and fibromyalgia.

OBJECTIVES: Tension-type headache (TTH) and fibromyalgia syndrome (FM) are worldwide seen chronic pain syndromes of unknown etiology. Despite the growing body of data on pathophysiology and generation mechanisms of pain; our knowledge on pain mechanisms in both FM and TTH is yet to be limited. PATIENTS AND METHODS: We investigated the plasma nitrite levels, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in 35 TTH, 33 FM patients and 31 healthy controls. RESULTS: The mean plasma nitrite levels and TAS levels were significantly low and OSI was found to be significantly high in TTH and FM groups compared to the control group (p=0.001, p=0.001, p=0.001 and p=0.001, respectively). The mean serum TOS levels were also significantly higher in FM group according to the control group (p=0.034), but there was not a significant difference between TTH and control groups (p=0.066). CONCLUSION: These results indicated that; FM and TTH patients revealed higher oxidative stress index and lower total nitrite levels than healthy controls. We conclude that oxidative stress may have a role in the pathophysiological mechanisms of TTH and FM, although, whether it is the cause or the consequence, is not clear.

Salivary cortisol and melatonin levels in children with frequent episodic tension-type headache do not differ from healthy children.

AIM: To investigate the differences in cortisol and melatonin concentrations between children with frequent episodic tension-type headache (FETTH) and healthy children. METHODS: Forty-four children, 12 boys/32 girls (age: 9 ± 2 years) with FETTH associated to peri-cranial tenderness and 44 age- and sex- matched healthy children participated. Both salivary cortisol and melatonin concentrations were collected from non-stimulated saliva following standardized guidelines. A headache diary for 4 weeks was used for collecting intensity, frequency and duration of headache. RESULTS: No significant differences for cortisol (t = -0.431; p = 0.668), and melatonin (z = -1.564; p = 0.118) concentrations and salivary flow rate (z = -1.190; p = 0.234) were found between both groups. No significant effect of age or gender was found. In addition, no significant association between cortisol-melatonin concentrations and between cortisol-melatonin concentrations and headache clinical parameters were found. CONCLUSION: These results suggest that children with FETTH, at first instance, do not present deficits in the secretion of these cortisol and melatonin. Prospective longitudinal studies are needed to further elucidate the direction of current findings, particularly the synchronism of cortisol and melatonin and the course of the headache.

Lower immunglobulin A levels but not lower cortisol or α-amylase activity in children with chronic tension-type headache.

OBJECTIVE: The study was designed to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), immunoglobulin A (IgA) (immune system) concentrations and α-amylase (sympathetic nervous system [SNS]) activity between children with chronic tension-type headache (CTTH) and healthy children. METHODS: Thirty-six children, 10 boys and 26 girls (age: 9 ± 2 years) with CTTH and 36 age- and sex-matched healthy children were recruited. Salivary cortisol, α-amylase activity, salivary flow rate, IgA concentration and IgA rate were collected from non-stimulated saliva. A headache diary was used for collecting data on intensity, frequency and duration of headache for four weeks. RESULTS: Children with CTTH showed lower IgA concentration (p = .008) and IgA rate (p = .039), but not lower cortisol concentration (p = .447), salivary flow rate (p = .289) or α-amylase activity (p = .559), as compared to healthy children. Neither age (p > .582) nor gender (p > .227) influenced salivary markers. A significant association between the number of years with headache and IgA concentration (r(s) = - 0.385; p = .023) was found: the greater the number of years with headache, the lower the IgA concentration. CONCLUSIONS: These results suggest that children with CTTH present with deficits in the immune system, but not dysfunction in the HPA axis or SNS. Future studies are needed to elucidate the direction of these relationships.

Tension-type headache and women: do sex hormones influence tension-type headache?

Most of the world's population has suffered from a tension-type headache (TTH) at some point in their lives. The pathophysiology of this disease is not well understood, but TTH shares many features with migraine, leading to the belief that TTH and migraine may be on different ends of the same disease spectrum. There are many shared triggers between migraine and TTH, menstruation being one of them. Does menses being a trigger for TTH make TTH more like migraine, or does the role of sex hormones in TTH give us insight into the unique pathophysiology of this disease? This article will review TTH, concentrating on the role of sex hormones as a trigger for TTH.

Inmigración y necesidades de asistencia psiquiátrica en población infanto-juvenil / No disponible

No disponible

[Effects of mirtazapine in patients with chronic tension-type headache. Literature review]. / A mirtazapin hatása a krónikus tenziós típusú fejfájásban szenvedõ betegekre. Irodalmi attekintés.

On the basis of the criteria of the International Headache Society (IHS) tension-type headache (TTH) is classed among the primary headaches. The independent headache diseases are characterized with the type of headache and with the concomitant symptoms. Among the independent headaches TTH has the highest prevalence (38.3%). The prevalence which is the highest between the age of 30 and 39, in women is higher (46,9%) than is men (42.3%). The diagnosis of TTH is not automatically mean the diagnosis of depression. Depression can occur as a comorbid disease. In episodic TTH the prevalence of depression is 32%, while in chronic TTH it is 40%. The prophylactic treatment of patients suffering from chronic TTH has not been solved yet. On the basis of a double-blind, placebo-controlled study mirtazapine is said to be a good opportunity in the treatment of patients with chronic TTH, as it improved the status of the patients with 34% (AUC: Area Under the headache Curve calculated from the product of the period and the intensity of headache), moreover mirtazapine decreased the frequency, intensity and duration of headache as well. The favourable effects of mirtazapine is explained beyond its serotonergic and noradrenergic dual mode of action with its antinociceptive effects which is presumably fulfilled via 3-opioid receptors.

Brainstem and cervical spinal cord Fos immunoreactivity evoked by nerve growth factor injection into neck muscles in mice.

Although myofascial tenderness is thought to play a key role in the pathophysiology of tension-type headache, very few studies have addressed neck muscle nociception. The neuronal activation pattern following local nerve growth factor (NGF) administration into semispinal neck muscles in anaesthetized mice was investigated using Fos protein immunohistochemistry. In order to differentiate between the effects of NGF administration on c-fos expression and the effects of surgical preparation, needle insertion and intramuscular injection, the experiments were conducted in three groups. In the sham group (n=7) cannula needles were only inserted without any injection. In the saline (n=7) and NGF groups (n=7) 0.9% physiological saline solution or 0.8 microm NGF solution were injected in both muscles, respectively. In comparison with sham and saline conditions, NGF administration induced significantly stronger Fos immunoreactivity in the mesencephalic periaqueductal grey (PAG), the medullary lateral reticular nucleus (LRN), and superficial layers I and II of cervical spinal dorsal horns C1, C2 and C3. This activation pattern corresponds very well to central nervous system processing of deep noxious input. A knowledge of the central anatomical representation of neck muscle pain is an essential prerequisite for the investigation of neck muscle nociception in order to develop a future model of tension-type headache.

Tension-type headaches: what they are and how to treat them.

Most clinicians and patients traditionally think of the tension-type headache (TTH) as the "unmigraine" or "nonmigraine." This view may be changing as distinctions between migraines and nonmigrainesdissolve. For many years, clinical diagnosis of TTH was based on nonthrobbing, bilateral pain. The mechanisms underlying the cause of TTH are still poorly understood. Some clinicians keep TTH and migraine in two separate clinical environments, while others see the two as a spectrum disorder with a common pathophysiology;however, there is not enough evidence to make anyone theory the clear-cut victor. Treatment strategies for TTH have evolved in favor of the patient. Newer categories of pharmacologic agents, often stabilizing to neuronal networks, are the modern mainstay of therapy for migraines and mixed headache disorders such as TTH.

Analgesic effect of amitriptyline in chronic tension-type headache is not directly related to serotonin reuptake inhibition.

The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension-type headache (CTTH). However, it is not fully clarified whether the serotonin (5-HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5-HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline we investigated platelet 5-HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty-four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5-HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32-week, double-blind, placebo-controlled, three-way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5-HT was used as a measure of 5-HT reuptake inhibition and determined by high performance liquid chromatography. Area under the headache curve was 308 (157-715) (median with quartiles in parentheses) with amitriptyline and significantly lower than 377 (158-1121) with citalopram (P = 0.04) and 441 (178-1408) with placebo (P = 0.002). There was no difference between citalopram and placebo (P = 0.23). Platelet 5-HT was 0.4 (0.3-0.7) x 10(-18)mol/platelet with citalopram, which was significantly lower than 1.7 (1.2-2.4) x 10(-18)mol/platelet with amitriptyline (P < 0.001), and 3.5 (2.8-4.3) x 10(-18)mol/platelet with placebo (P < 0.001). The lower platelet 5-HT during treatment with citalopram than amitriptyline indicates that 5-HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5-HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research.

Tender points are not sites of ongoing inflammation -in vivo evidence in patients with chronic tension-type headache.

Increased muscle tenderness is the most prominent finding in patients with tension-type headache, and it has recently been shown that muscle blood flow is diminished in response to static exercise in tender points in these patients. Although tenderness has been ascribed to local inflammation and release of inflammatory mediators, the interstitial concentration of inflammatory mediators has not previously been studied in tender muscles of patients with tension-type headache. The aim of the present study was to investigate in vivo concentrations of prostaglandin E2 (PGE2), adenosine 5'-triphosphate (ATP), glutamate, bradykinin and other metabolites in a tender point of patients with chronic tension-type headache, in the resting state as well as in response to static exercise, and to compare findings with measurements in a matched non-tender point of healthy controls. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle and dialysates were collected at rest, 15 and 30 min after start of static exercise (10% of maximal force) and 15 and 30 min after end of exercise. All samples were coded and analysed blindly. There was no difference in resting concentration of any inflammatory mediators or metabolites between tender patients and non-tender controls (P > 0.05). We also found no difference in change in interstitial concentration of ATP, PGE2, glutamate, glucose, pyruvate and urea from baseline to exercise and post-exercise periods between patients and controls (P > 0.05). The present study provides in vivo evidence of normal interstitial levels of inflammatory mediators and metabolites in tender trapezius muscle in patients with chronic tension-type headache during both rest and static exercise. Thus, our data suggest that tender points in these patients are not sites of ongoing inflammation.

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.

The effect of acupuncture on proinflammatory cytokine production in patients with chronic headache: a preliminary report.

Acupuncture has been widely used as a treatment for various conditions like headache and stroke, especially in Asian countries such as Korea and China. But few scientific investigations have been carried out. The aim of the present study is to investigate the effect of acupuncture on the production of inflammatory cytokines in patients with chronic headache (CH). Patients with CH were treated with acupuncture during the acute stage. Clinical signs of CH disappeared markedly after three months of treatment with acupuncture. Peripheral blood mononuclear cells obtained from a normal group and those from the patients with CH, before and after treatment with acupuncture, were cultured for 24 hours in the presence or absence of lipopolysaccharide (LPS). The amount of interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) in LPS culture supernatant was significantly increased in the patients with CH compared to the healthy control group (p < 0.05). But those cytokines came down toward the levels of the healthy group (p < 0.05) after treatment with acupuncture, although the levels still remained elevated. Plasma cytokine levels were analyzed to evaluate any change due to acupuncture treatment. There was little difference in the levels of IL-1 or IL-6 due to the treatment with acupuncture in the patients with CH, but significantly reduced plasma levels of TNF-alpha were observed. These data suggest that acupuncture treatment has an inhibitory effect on pro-inflammatory cytokine production in patients with CH.