Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study.

BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

Does menstruation-related headache occur exclusively in women with migraine?

To determine the relation between headache and menstruation in women with migraine and the use of estrogen by these women. This was a prospective, cross-sectional, observational study with group comparison, using non-random sample and convenience. We interviewed 79 women diagnosed with migraine or tension-type headache (TTH), according to the ICHD-3, regarding the relation between headache and menstruation. Of the 79 women with headache, 60 (76%) had migraine and 19 (24%) had episodic TTH. The most frequent subtype of migraine was without aura (54/60, 90%). The age ranged from 18 to 42 years, with an average of 22.6 ± 4.1 years. Migraine affected women aged 22.4 ± 3.6 years, whereas in TTH, the age was 23.0 ± 5.4 years. Menstruation-related headache occurred in 41.9% of women with migraine and in only 6.3% of those with TTH. These differences were significant (χ2 = 5.2; p = 0.022). Of the five women diagnosed with migraine with aura, two used estrogen. Menstruation-related headache predominates in women with migraine and often women with migraine with aura use estrogen.

Comparison of Thrombocyte Count Between Pediatric Patients With Migraine or Tension-Type Headache: A Retrospective Cohort Study.

Hypercoagulability may explain the increased risk of thromboembolic cerebrovascular events in patients with migraine. Thrombocytes play a crucial part in the coagulation process, and some studies have demonstrated hyperaggregation of thrombocytes in adult migraineurs. We aimed to compare thrombocyte count between pediatric patients with migraine or tension-type headache and to evaluate the correlation of thrombocyte count with headache parameters. The electronic database of a tertiary pediatric headache clinic was retrospectively searched for all children and adolescents diagnosed with migraine or tension-type headache in 2016-2018. Data on thrombocyte counts were collected from the medical files and compared between the groups by parametric and nonparametric statistical tests. The cohort included 299 patients, 176 girls (59.0%) and 123 (412.0%) boys, of mean age 12.2 ± 3.4 years; 198 had migraine and 101 had tension-type headache. Among the laboratory parameters evaluated, a significantly lower mean thrombocyte number was found in the migraine group than in the tension-type headache group (282 ± 60 vs 304±71 ×103/µL, P = .004). Within the migraine group, there was a significant negative correlation between the thrombocyte count and the duration of headache attacks in hours (P < .05). No significant between- or within-group differences were found in other laboratory parameters. The low relative thrombocyte count in pediatric headache clinic patients with migraine and its negative correlation with duration of migraine suggest that migraine may be associated with a different underlying pathogenesis from tension-type headache.

BDNF and serum S100B levels according the spectrum of structural pathology in chronic pain patients.

Central sensitivity syndrome (CSS) consists of adaptive pathophysiological changes associated with neuroplasticity in some chronic pain disorders. It could be grouped in two main conceptual conditions: one includes those chronic pain patients without overt structural pathology such as fibromyalgia, and the other subgroup includes conditions with recognizable structural abnormalities, both somatic (osteoarthritis) and visceral (endometriosis). In order to understand the role of neuromodulators in CCS we aim to determine whether brain-derived neurotrophic factor (BDNF) and S100B are associated to specific chronic pain disorders. Serum BDNF and S100B were measured in chronic pain women with different diagnosis: 88 with osteoarthritis, 36 with endometriosis, 117 with fibromyalgia, 33 with chronic tension type headache and in 41 healthy controls. ANCOVA analysis followed by heteroscedasticity-consistent covariance matrix was performed to evaluate BDNF and S100B levels, adjusted for depression severity, pain levels and use of analgesics according different pathologies. Serum BDNF concentrations were higher and not different in patients with fibromyalgia and headache, the CSS group without structural pathology. In contrast, the concentrations of S100B were higher in patients with osteoarthritis and endometriosis, in comparison to controls, fibromyalgia and tensional headache patients. This study supports the hypothesis that BDNF and S100B neuromodulators present different serum levels according to the background disease associated to the chronic pain. These have the potential to be studied as markers of active disease or treatment evolution.

Male and female sex hormones in primary headaches.

BACKGROUND: The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence. These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches. This review aims to summarise the most relevant and recent literature on this topic. METHODS: Two independent reviewers searched PUBMED in a systematic manner. Search strings were composed using the terms LH, FSH, progesteron*, estrogen*, DHEA*, prolactin, testosterone, androgen*, headach*, migrain*, "tension type" or cluster. A timeframe was set limiting the search to articles published in the last 20 years, after January 1st 1997. RESULTS: Migraine tends to follow a classic temporal pattern throughout a woman's life corresponding to the fluctuation of estrogen in the different reproductive stages. The estrogen withdrawal hypothesis forms the basis for most of the assumptions made on this behalf. The role of other hormones as well as the importance of sex hormones in other primary headaches is far less studied. CONCLUSION: The available literature mainly covers the role of sex hormones in migraine in women. Detailed studies especially in the elderly of both sexes and in cluster headache and tension-type headache are warranted to fully elucidate the role of these hormones in all primary headaches.

Distinguishing neurocysticercosis epilepsy from epilepsy of unknown etiology using a minimal serum mass profiling platform.

Neurocysticercosis is associated with epilepsy in pig-raising communities with poor sanitation. Current internationally recognized diagnostic guidelines for neurocysticercosis rely on brain imaging, a technology that is frequently not available or not accessible in areas endemic for neurocysticercosis. Minimally invasive and low-cost aids for diagnosing neurocysticercosis epilepsy could improve treatment of neurocysticercosis. The goal of this study was to test the extent to which patients with neurocysticercosis epilepsy, epilepsy of unknown etiology, idiopathic headaches and among different types of neurocysticercosis lesions could be distinguished from each other based on serum mass profiling. For this, we collected sera from patients with neurocysticercosis-associated epilepsy, epilepsy of unknown etiology, recovered neurocysticercosis, and idiopathic headaches then performed binary group comparisons among them using electrospray ionization mass spectrometry. A leave one [serum sample] out cross validation procedure was employed to analyze spectral data. Sera from neurocysticercosis patients was distinguished from epilepsy of unknown etiology patients with a p-value of 10-28. This distinction was lost when samples were randomized to either group (p-value = 0.22). Similarly, binary comparisons of patients with neurocysticercosis who has different types of lesions showed that different forms of this disease were also distinguishable from one another. These results suggest neurocysticercosis epilepsy can be distinguished from epilepsy of unknown etiology based on biomolecular differences in sera detected by mass profiling.

The association between serum vitamin B12 deficiency and tension-type headache in Turkish children.

This study aimed to determine the relationship between serum vitamin B12 level and tension-type headache. The study groups consisted of 75 patients (40 females, 35 males) with headache and a control group of 49 healthy children (25 females, 24 males). Serum vitamin B12 level < 200 pg/ml was defined as deficient, and < 160 pg/ml as severely deficient. The serum vitamin B12 level was measured by the electrochemiluminescence (ECLIA) method. The serum vitamin B12 levels in the headache and control groups were 273.01 ± 76.77 and 316.22 ± 74.53 pg/ml, with the difference determined as statistically significant (p = 0.003). In the case group, 18/75 patients (24%) had a serum vitamin B12 level below the normal of 200 pg/ml, and in the control group 4/49 (8%) patients were also below the normal range (p = 0.021). The serum vitamin B12 level in the children with tension-type headache was significantly lower than that in the control group. From the results of the study, it was concluded that there may be an association between vitamin B12 level and tension-type headache. However, further clinical studies are needed.

Accompanying migrainous features in pediatric migraine patients with restless legs syndrome.

The present study aimed to examine the frequency of restless legs syndrome (RLS) in pediatric patients with migraine and tension-type headache (TTH) and to investigate accompanying migrainous symptoms, sleep characteristics, as well as levels of serum ferritin between the pediatric migraine patients with RLS and those without RLS. We included 65 consecutive patients diagnosed with migraine, 20 patients with TTH, and 97 headache-free children in our study. Demographic, clinical, and laboratory data were noted. The presence of a primary headache was diagnosed using the ICHD-II criteria, and RLS was determined with face-to-face interviews conducted by an experienced neurologist based on the revised International RLS Study Group criteria for pediatrics. The frequency of RLS in pediatric migraine and TTH patients was significantly higher than in the controls (p = 0.0001 and p = 0.025, respectively). The frequencies of allodynia, vertigo/dizziness, and self-reported frequent arousals were significantly higher, and serum ferritin levels were significantly lower in migraine patients with RLS compared to those without RLS (p = 0.05, p = 0.028, p = 0.02, and p = 0.038, respectively). Our study suggests that the frequency of RLS is higher in pediatric migraine and TTH patients compared to controls. Therefore, pediatric headache patients should be questioned about the presence of RLS, as this co-occurrence may lead to more frequent accompanying migrainous symptoms and sleep disturbances.

Vitamin D Deficiency in Patients With Chronic Tension-Type Headache: A Case-Control Study.

OBJECTIVE: To see the interrelation between chronic tension-type headache (CTTH) and serum vitamin D levels. BACKGROUND: Several studies have suggested an association between chronic pain and vitamin D deficiency. Anecdotal evidence suggests that vitamin D deficiency may be associated with tension-type headache and migraine. METHODS: This case-control study was carried out to examine the association between CTTH and serum 25-hydroxy vitamin (25(OH) D) levels. One hundred consecutive adult (>18 years) patients with CTTH and 100 matched healthy controls were enrolled. RESULTS: The serum 25(OH) D levels were significantly lower in CTTH patients than in the controls (14.7 vs 27.4 ng/mL). The prevalence of vitamin D deficiency (serum 25 (OH) D < 20 ng/mL) was greater in patients with CTTH (71% vs 25%). CTTH patients had a significantly high prevalence of musculoskeletal pain (79% vs 57%), muscle weakness (29%vs 10%), muscle tenderness score (7.5 vs 1.9), and bone tenderness score (3.0 vs 0.8) in comparison to controls. CTTH patients with vitamin D deficient group (<20 ng/mL) had a higher prevalence of musculoskeletal pain (58% vs 31%), muscle weakness (38%vs 7%), muscle and bone tenderness score, associated fatigue (44% vs 17%) and more prolonged course (15.5 months vs 11.2 months). A strong positive correlation was noted between serum vitamin D levels and total muscle tenderness score (R2 = 0. 7365) and total bone tenderness score (R2 = 0. 6293). CONCLUSION: Decreased serum 25(OHD) concentration was associated with CTTH. Intervention studies are required to find out if supplementation of vitamin D is effective in patients with CTTH.

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients.

OBJECTIVES: Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. METHODS: This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. RESULTS: We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. CONCLUSIONS: This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients / Níveis séricos de adiponectina, CCL3/MIP-1α, and CCL5/RANTES discriminam pacientes com migrânea e cefaleia do tipo tensional

ABSTRACT Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.

RESUMO Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.

Interictal plasma pituitary adenylate cyclase-activating polypeptide levels are decreased in migraineurs but remain unchanged in patients with tension-type headache.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is associated with migraine phase; however, whether PACAP levels could be used to distinguish between migraine and tension-type headache (TTH) remains unknown. We compared interictal plasma PACAP levels among healthy controls, migraineurs, and patients with TTH. METHODS: Interictal plasma levels of PACAP were measured in 133 migraineurs, 106 patients with TTH, and 50 controls using enzyme-linked immunoassays. We further evaluated the relationships between interictal PACAP plasma concentrations and clinical parameters, such as headache severity, attack frequency, and duration. RESULTS: We found that migraineurs had significantly lower interictal plasma PACAP levels than patients with TTH and healthy controls. However, there were no significant differences between patients with TTH and healthy controls. Plasma PACAP levels were significantly lower in patients with episodic migraine (EM) than in patients with episodic tension-type headache (ETTH) and in patients with chronic migraine (CM) than in patients with chronic tension-type headache (CTTH). Interictal PACAP levels were negatively correlated with duration in the CM group. CONCLUSIONS: The results of this study demonstrated differences in interictal PACAP levels in migraine and TTH, suggesting that PACAP is involved in the pathogenesis of migraine rather than TTH.

Neurotrophic factors in tension-type headache.

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Serum oxidant and antioxidant status of patients with chronic tension-type headache: possible effects of medical treatment.

Tension-type headache (TTH) is one of the most common and costly primary types of headache in clinical practice, with an unknown etiology. This study assessed to investigate oxidative and antioxidative status in patients with chronic tension-type headache (CTTH), and to evaluate possible effect of medical treatment. The study included 41 CTTH patients and 19 age- and sex-matched healthy subjects without headache as controls. The CTTH group comprised 20 patients receiving treatment and 21 untreated patients. We evaluated oxidant/antioxidant status by measuring serum malondialdehyde (MDA) levels and activities of antioxidant enzymes, namely glutathione peroxidase (GSH-Px) and catalase (CAT). Comparison of oxidative parameters in the patient and control groups revealed significantly lower CAT activities and higher MDA level and GSH-Px activities in the patient group. In the CTTH group, serum CAT activities were found to be significantly decreased in patient groups, while serum MDA levels and GSH-Px activities were found to be higher in the untreated CTTH patients. These findings suggest that oxidative stress is increased in the patients with CTTH, and medical treatment abolishes the stress in part. It has been concluded that antioxidant support might be helpful for the patients with CTTH to prevent oxidant stress and peroxidation damages further.

Electroacupuncture analgesia is associated with increased serum brain-derived neurotrophic factor in chronic tension-type headache: a randomized, sham controlled, crossover trial.

BACKGROUND: Chronic tension-type headache (CTTH) is characterized by almost daily headaches and central sensitization, for which electroacupuncture (EA) might be effective. The central nervous system (CNS) plasticity can be tracked in serum using the brain-derived neurotrophic factor (BDNF), a neuroplasticity mediator. Thus, we tested the hypothesis that EA analgesia in CTTH is related to neuroplasticity indexed by serum BDNF. METHODS: We enrolled females aged 18-60 years with CTTH in a randomized, blinded, placebo-controlled crossover trial, comparing ten EA sessions applied for 30 minutes (2-10 Hz, intensity by tolerance) in cervical areas twice per week vs. a sham intervention. Treatment periods were separated by two washout weeks. Pain on the 10-cm visual analog scale (VAS) and serum BDNF were assessed as primary outcomes. RESULTS: Thirty-four subjects underwent randomization, and twenty-nine completed the protocol. EA was superior to sham to alleviate pain (VAS scores 2.38 ± 1.77 and 3.02 ± 2.49, respectively, P = 0.005). The VAS scores differed according to the intervention sequence, demonstrating a carryover effect (P < 0.05). Using multiple regression, serum BDNF was adjusted for the Hamilton depression rating scale (HDRS) and the VAS scores (r-squared = 0.07, standard ß coefficients = -0.2 and -0.14, respectively, P < 0.001). At the end of the first intervention period, the adjusted BDNF was higher in the EA phase (29.31 ± 3.24, 27.53 ± 2.94 ng/mL, Cohen's d = 0.55). CONCLUSION: EA analgesia is related to neuroplasticity indexed by the adjusted BDNF. EA modulation of pain and BDNF occurs according to the CNS situation at the moment of its administration, as it was related to depression and the timing of its administration.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Reduced serum levels of adiponectin in tension-type headache.

BACKGROUND AND OBJECTIVES: Inflammatory mediators have been studied in tension type headache (TTH) pathophysiology; however, their role is not yet well established. The aim of the present study was to investigate adiponectin (ADP) and its association with clinical parameters and psychiatric comorbidities in TTH patients. METHODS: This was a cross sectional study including TTH patients and controls. Beck Depression (BDI) and Anxiety (BAI) Inventories, and Headache Impact Test (HIT-6) were recorded. Serum levels of ADP were measured by ELISA. RESULTS: Forty-eight TTH patients and forty-eight controls without headache were enrolled in the study. ADP levels were significantly lower among patients with TTH [31.1 (20.4-69.20) versus 37.8 (24.9-71.4) ng/mL (P=0.008)]. ADP levels were not influenced by BDI and BAI scores, body mass index (BMI), or HIT-6. CONCLUSION: ADP levels were reduced in TTH, independently of psychiatric comorbidities, BMI, and headache impact.

Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology.

BACKGROUND AND OBJECTIVES: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility. METHODS: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37). RESULTS: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%). CONCLUSION: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Increased serum levels of interleukin-8 in patients with tension-type headache.

BACKGROUND AND OBJECTIVES: The pathophysiology of tension-type headache is not well understood. Increased peripheral levels of pro-inflammatory cytokines may act as mediators of several chronic pain disorders. The aim of the present study was to investigate the peripheral levels of chemokines in patients with tension-type headache. METHODS: This was a cross sectional study evaluating serum levels of chemokines in age and sex-matched tension-type headache patients, ictally and interictally, and control participants. Beck Depression and Anxiety Inventories were recorded. Serum levels of monocyte chemoattractant protein-1, macrophage inflammatory protein 1α, regulated on activation, normal T cell expressed and secreted, eotaxin, eotaxin-2, interleukin-8, interferon gamma induced protein-10 were measured by enzyme-linked immunosorbent assay. RESULTS: A total of 96 participants (48 tension-type headache, 48 controls) were included. Interleukin-8 levels were significantly increased in patients with tension-type headache when compared to controls (413.8 (123.4-1756.3) and 329 (107.8-955.6), respectively, P = 0.025). Anxiety and depression scores were higher in patients with tension-type headache but interleukin-8 increase in tension-type headache patients persisted after controlling for anxiety and depression symptoms. Patients with headache at the time of assessment had increased monocyte chemoattractant protein-1 levels when compared with patients without headache (2809.3 (1101-6122.2) and 1630.2 (669.3-31056.8), respectively P = 0.026). Patients with episodic and chronic tension-type headache had no significant differences in serum chemokines levels. CONCLUSION: Interleukin-8 was increased in tension-type headache and monocyte chemoattractant protein-1 was higher in tension-type headache patients with headache, suggesting that pro-inflammatory mechanisms may participate in tension-type headache pathophysiology.

Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache.

The primary aim of this study (TA-CH, Tryptophan Amine in Chronic Headache) was to investigate a possible role of tryptophan (TRP) metabolism in chronic migraine (CM) and chronic tension-type headache (CTTH). It is not known if TRP metabolism plays any role in CM and/or CTTH. Plasma levels of serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), metabolite of 5-HT, and tryptamine (TRY) were tested in 73 patients with CM, 15 patients with CTTH and 37 control subjects. Of these, plasmatic TRY was significantly lower in CM (p < 0.001) and in CTTH (p < 0.002) patients with respect to control subjects, while 5-HIAA levels in plasma were within the same range in all groups. 5-HT was undetectable in the plasma of almost all subjects. Our results support the hypothesis that TRP metabolism is altered in CM and CTTH patients, leading to a reduction in plasma TRY. As TRY modulates the function of pain matrix serotonergic system, this may affect modulation of incoming nociceptive inputs from the trigeminal endings and posterior horns of the spinal cord. We suggest that these biochemical abnormalities play a role in the chronicity of CM and CTTH.