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.

Headache in systemic lupus erythematosus: results from a prospective, international inception cohort study.

OBJECTIVE: To examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). METHODS: A disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. RESULTS: Among the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean ± SD age was 34.6 ± 13.4 years, duration of disease was 5.6 ± 5.2 months, and length of followup was 3.8 ± 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean ± SD 42.5 ± 12.2 versus 47.8 ± 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 ± 11.0 in those with headache versus 42.6 ± 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. CONCLUSION: Headache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies.

Interleukin-6 levels in tension headache patients.

OBJECTIVE: Cytokines are pain mediators in neurovascular inflammation. This study examined interleukin 6 (IL-6) levels in the serum of tension-type headache (TTH) patients, to determine if inflammation plays a role in the pathogenesis of this condition. METHODS: Serum IL-6 levels were studied in 42 patients and 37 healthy controls from the same region. Of the patients, 20 (47.6%) experiencing TTH less than 15 days per month were placed in episodic tension-type headache (ETTH) group, and 22 (52.3%) with TTH more than 15 days per month were placed in chronic tension-type headache (CTTH) group. RESULTS: The IL-6 level was significantly higher in the patients than in the controls. The IL-6 level of CTTH patients was higher than the controls (P<0.01). The IL-6 level was similar between ETTH and CTTH patients. Correlation analysis revealed a positive relationship only between age and IL-6 level in the patients. CONCLUSIONS: CTTH and ETTH patients had an elevated serum IL-6 level compared with controls. Therefore, we believe that IL-6 may be involved in pain induction or inflammatory mechanisms in TTH. Furthermore studies of the possible connection between chronicity of headaches and cytokine levels are needed.

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.

[Proinflammatory cytokines in children with idiopathic headache]. / Cytokiny prozapalne u dzieci z samoistnymi bólami glowy.

OBJECTIVES: The pathogenesis of primary headaches is differential, with a neurogenic inflammation participation. THE AIM: The aim of this research was to establish whether inflammation participates in the pathogenesis of migraine and tension-type headaches (ETTH). In order to establish this, the levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1beta), tumor necrosis factor (TNF) and soluble TNF receptor type I (sTNFRI) were detected in groups with headaches during headache-free interval and in controls and in the blood of children with idiopathic headaches to detect changes during headache attack. MATERIAL AND METHODS: 30 children with migraine were included (16 with aura and 14 without aura), 17 boys and 13 girls aged 10-17 years (mean 13.5). The group with ETTH consisted of 31 patients, 24 girls and 7 boys, aged 6-17 years (mean 13.5). The control group, 28 children without headache, diagnosed with non-inflammatory orthopedic diseases, consisted of 15 boys and 13 girls, aged 7-17 years (mean 13.0). When the pain started during hospitalization, the blood was sampled in the first hour of the headache, then 3 hours and 6 hours since headache started (if headache persisted), and 6 hours after its termination. Two days after the pain termination, the blood samples were collected in children suffering from headaches, as the headache-free measurements and in controls under the same conditions at 7 a.m. after awakening. The cytokine level was established using Biosource kits, all 326 samples were processed. The statistical assessment was conducted. RESULTS: No differences were detected in cytokine levels between the groups with migraine and ETTH and with comparison to controls during headache-free interval and during headache attack as well. However, it was established that in 12/30 children with migraine there was a significant increase in IL-6 level in the first hour of the migraine attack. This group consisted of 12 children with TNF level higher and the tendency toward decrease in sTNFRI was established, 3 hours since headache started, as compared to 18/30 children with migraine but without increase in IL-6. The correlation between the level of cytokines and age and weight was not detected. Also no correlation was established between cytokine levels and leukocyte and thrombocyte count. CONCLUSION: 1. Changes of the level of IL-6, IL-1beta, TNF and sTNFRI in the blood of children with idiopathic headache do not indicate a significant role of inflammatory process in its pathogenesis. 2. Although the significant increase in IL-6 levels observed in several children in the first hour of the migraine attack may suggest that neurogenic inflammation participates in the pathogenesis of migraine.

[Blood interleukin-6 level in children with idiopathic headaches]. / Stezenie interleukiny-6 we krwi u dzieci z samoistnymi bólami glowy.

AIM: Neurogenic inflammation may contribute to the pathogenesis of migraine. IL-6 plays an important role as a proinflammatory cytokine. The aim of this research was to investigate IL-6 level changes in children with migraine and episodic tension-type headache (ETTH) at baseline and during a headache attack, and also factors which may influence these changes (aura, sex, weight, leukocyte and thrombocyte count). MATERIALS AND METHODS: In 30 children with migraine, 31 with ETTH and 28 controls without headaches, an IL-6 level was established in plasma using Biosource kit in the first, third and sixth hour of headache, and 6 hours after its termination. Two days after pain termination, the headache-free measurements were analyzed, and under the same conditions in controls. A statistical assessment was performed. RESULTS: In 12/30 children with migraine there was an increase in the IL-6 level in the first hour of the attack. There were no differences between migraine with and without aura, migraine and ETTH, and between headaches at baseline and controls. There was an increase in the IL-6 level in children with prolonged primary headaches (migraine and ETTH) in the third and sixth hour of the attack. No correlation between IL-6 and sex, count of leukocytes and thrombocytes was established. CONCLUSION: The increase in the IL-6 level in several children with migraine in the first hour of the attack may suggest that neurogenic inflammation contributes to the migraine pathogenesis. IL-6 is not involved in the pathogenesis of ETTH. The increase in the IL-6 level in children with prolonged headache may reflect a stress reaction.