Immunological findings in patients with migraine and other primary headaches: a narrative review

Abstract Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the Human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.

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Crying as a precipitating factor for migraine and tension-type headache

Sao Paulo Medical Journal ◽

10.1590/s1516-31802003000100008 ◽

2003 ◽

Vol 121 (1) ◽

pp. 31-33 ◽

Cited By ~ 4

Author(s):

Yara Dadalti Fragoso ◽

Regina Carvalho ◽

Fernanda Ferrero ◽

Darcya Maria Lourenço ◽

Erica Regina Paulino

Keyword(s):

Daily Practice ◽

Tension Type Headache ◽

Primary Headaches ◽

Precipitating Factors ◽

Headache Type ◽

Potential Factor ◽

Type Headache ◽

One Year ◽

Precipitating Factor

CONTEXT: Scarcely reported in the literature, crying seems to be an important precipitating factor for both migraine and tension-type headache in daily practice. OBJECTIVE: To evaluate the role of crying as a precipitating factor for migraine and tension-type headache. TYPE OF STUDY: Prospective evaluation. PARTICIPANTS: 163 workers or students from the Universidade Metropolitana de Santos, who presented at least one attack a month, for at least one year, of either migraine or tension-type headache. PROCEDURES: Interview by means of questionnaires and personal evaluations. Details of precipitating factors for the attacks were assessed. RESULTS: From the total group of 163 individuals, 90 (55.2%) considered crying to be a potential factor for triggering headache attacks. Of this group of 90 persons, 62 presented migraine (6 males, 56 females) and 28 presented tension-type headache (5 males, 23 females). Only stress, anxiety and menstrual periods rated higher or equal to crying as triggering factors for both types of headache. CONCLUSIONS: The physiology of crying is not well documented or understood. The act of crying seems to be an important precipitating factor for primary headaches and it should be studied further. The authors welcome comments on the matter and would like to work in collaboration with other groups interested in this subject.

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Neuroimaging in Outpatients with Tension Type Headache

Galen Medical Journal ◽

10.31661/gmj.v4i2.308 ◽

2015 ◽

Vol 4 (2) ◽

pp. 62-66

Author(s):

Peyman Petramfar ◽

Sajad Pishgar

Keyword(s):

Prospective Study ◽

Tension Type Headache ◽

Primary Headaches ◽

Neurological Exam ◽

Type Headache ◽

A Prospective Study ◽

New Onset

Background: Research into the role of neuroimaging in primary headaches such as tension type headache (TTH) is ongoing. In the present study, we aim to evaluate the ability of neuroimaging to detect potential abnormalities in patients with new onset TTH and normal neurological exam. Materials and Methods: In a prospective study, 294 cases of new onset TTH with normal neurological exam, that had neuroimaging, were selected. Imaging was evaluated for significant abnormalities. The percentage of abnormal findings in imaging was calculated. Results: 64(21.8%) patients had MRI. Of them, 21.8% of MRIs revealed abnormal findings. Meanwhile, from 238 CTs, only 0.4% showed abnormalities. Conclusion: Neuroimaging with current quality does not play an important role in management of patients with new onset TTH and normal neurological exam. [GMJ.2015;4(2):62-66]

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CGRP in human models of primary headaches

Cephalalgia ◽

10.1177/0333102416684344 ◽

2016 ◽

Vol 38 (2) ◽

pp. 353-360 ◽

Cited By ~ 7

Author(s):

Håkan Ashina ◽

Henrik Winther Schytz ◽

Messoud Ashina

Keyword(s):

Treatment Strategies ◽

Primary Headache ◽

Experimental Models ◽

Tension Type Headache ◽

Primary Headaches ◽

Human Models ◽

New Treatment ◽

Type Headache ◽

Methodological Aspects

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.

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Quality of life in primary headaches and biofeedback effects

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2010-2-34-37 ◽

2010 ◽

Vol 9 (2) ◽

pp. 34-37

Author(s):

N. L. Starikova

Keyword(s):

Quality Of Life ◽

Coping Strategies ◽

Tension Type Headache ◽

Anxiety And Depression ◽

Primary Headaches ◽

Strongly Correlated ◽

Passive Coping ◽

Type Headache ◽

Headache Patients

Determinants of quality of life (QoL) in primary headaches remain unclear. We studied QoL in 107 patients (50 migraine patients, 57 tension-type headache — TTH-patients) and 10 healthy subjects. QoL in headache patients was reduced and strongly correlated with passive coping strategies preference, levels of anxiety and depression. In migraine QoL depended on duration of the disease, intensity of pain and MIDAS score. In TTH no clinical features of the disease influenced QoL. Biofeedback showed high effectiveness in primary headaches which depended on coping strategies of patients.

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Prevalence of Primary Headaches in People with Multiple Sclerosis

Cephalalgia ◽

10.1111/j.1468-2982.2004.00790.x ◽

2004 ◽

Vol 24 (11) ◽

pp. 980-984 ◽

Cited By ~ 68

Author(s):

D D'Amico ◽

L La Mantia ◽

A Rigamonti ◽

S Usai ◽

N Mascoli ◽

...

Keyword(s):

Multiple Sclerosis ◽

International Headache Society ◽

Primary Headache ◽

Tension Type Headache ◽

Primary Headaches ◽

Exact Test ◽

Relapsing Remitting ◽

Type Headache ◽

Ms Therapy

The aim was to investigate the lifetime prevalence of headache and primary headache (diagnoses according to International Headache Society criteria) in multiple sclerosis (MS). The relationships between headache and clinical features of MS and MS therapy were also investigated. We studied 137 patients with clinically definite MS; 88 reported headache, 21 of whom developed headache after the initiation of interferon. The prevalence of all headaches in the remaining 116 patients was 57.7%. Migraine was found in 25.0%, tension-type headache in 31.9%, and cluster headache in one patient. A significant correlation ( P = 0.007, Fisher's exact test) between migraine and relapsing-remitting MS was found. Primary headaches are common in MS patients. Further studies are needed to clarify the mechanisms underlying this association, particularly the association between migraine and relapsing-remitting MS, and the role of interferon in the development of new headache.

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Osmophobia in primary headache patients: associated symptoms and response to preventive treatments

The Journal of Headache and Pain ◽

10.1186/s10194-021-01327-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Marianna Delussi ◽

Anna Laporta ◽

Ilaria Fraccalvieri ◽

Marina de Tommaso

Keyword(s):

Cluster Headache ◽

Rating Scale ◽

Preventive Treatment ◽

Primary Headache ◽

Tension Type Headache ◽

Primary Headaches ◽

Self Rating ◽

Type Headache ◽

Headache Center ◽

Headache Patients

Abstract Background Osmophobia, is common among primary headaches, with prevalence of migraine. The study aimed to evaluate prevalence and clinical characteristics of patients with osmophobia in a cohort of primary headache patients selected at a tertiary headache center. The second aim was to verify the possible predicting role of osmophobia in preventive treatment response in a sub cohort of migraine patients. Methods This was an observational retrospective cohort study based on data collected in a tertiary headache center. We selected patients aged 18–65 years, diagnosed as migraine without aura (MO), migraine with aura (MA) or Chronic Migraine (CM), Tension-Type Headache (TTH); and Cluster Headache (CH). We also selected a sub-cohort of migraine patients who were prescribed preventive treatment, according to Italian Guidelines, visited after 3 months follow up. Patients were considered osmophobic, if reported this symptom in at least the 20% of headache episodes. Other considered variables were: headache frequeny, the migraine disability assessment (MIDAS), Allodynia Symptom Checklist, Self-rating Depression scale, Self-rating Anxiety scale, Pain intensity evaluated by Numerical Rating Scale-NRS- form 0 to 10. Results The 37,9% of patients reported osmophobia (444 patients with osmophobia, 726 without osmophobia). Osmophobia prevailed in patients with the different migraine subtypes, and was absent in patients with episodic tension type headache and cluster headache (chi square 68.7 DF 7 p < 0.0001). Headache patients with osmophobia, presented with longer hedache duration (F 4.91 p 0.027; more severe anxiety (F 7.56 0.007), depression (F 5.3 p 0.019), allodynia (F 6 p 0.014), headache intensity (F 8.67 p 0.003). Tension type headache patients with osmophobia (n° 21), presented with more frequent headache and anxiety. A total of 711 migraine patients was visited after 3 months treatment. The change of main migraine features was similar between patients with and without osmophobia. Conclusions While the present study confirmed prevalence of osmophobia in migraine patients, it also indicated its presence among chronic tension type headache cases, marking those with chronic headache and anxiety. Osmophobia was associated to symptoms of central sensitization, as allodynia. It was not relevant to predict migraine evolution after first line preventive approach.

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Calcitonin Gene-Related Peptide in Tension-Type Headache

The Scientific World JOURNAL ◽

10.1100/tsw.2002.808 ◽

2002 ◽

Vol 2 ◽

pp. 1527-1531 ◽

Cited By ~ 3

Author(s):

M. Ashina

Keyword(s):

Plasma Levels ◽

Calcitonin Gene Related Peptide ◽

Tension Type Headache ◽

Nerve Fibers ◽

Primary Headaches ◽

Chronic Tension Type Headache ◽

Related Peptide ◽

Calcitonin Gene ◽

Type Headache

In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP) in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tension-type headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles) levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache.

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Intravenous Metamizol (Dipyrone) in Acute Migraine Treatment and in Episodic Tension-Type Headache–A Placebo-Controlled Study

Cephalalgia ◽

10.1046/j.1468-2982.2001.00143.x ◽

2001 ◽

Vol 21 (2) ◽

pp. 90-95 ◽

Cited By ~ 31

Author(s):

ME Bigal ◽

CA Bordini ◽

JG Speciali

Keyword(s):

Migraine With Aura ◽

Migraine Without Aura ◽

Good Alternative ◽

Tension Type Headache ◽

Controlled Study ◽

Migraine Treatment ◽

Primary Headaches ◽

Emergency Rooms ◽

Type Headache ◽

Headache Patients

Acute headache is a very frequent symptom, responsible for significant demand at primary care units and emergency rooms. In such sets in Brazil, metamizol is easily found but, on the other hand, neither ergotics nor triptans are available. The aim of this study is to compare intravenous metamizol with placebo in the acute treatment of migraine with aura, migraine without aura and episodic tension-type headache. Fifty-four migraine with aura patients, 95 migraine without aura patients and 30 tension-type headache patients were treated with metamizol. Ninety patients (30 migraine with aura, 30 migraine without aura and 30 tension-type headache patients) received placebo. Pain intensity, nausea, aura, photo- and phonophobia were investigated at 30 min and 60 min after the administration of the drug. Significant improvement of pain after 30 min and 60 min post-dosage was achieved from metamizol groups compared with placebo groups. Significant improvement of all other symptoms was achieved after 60 min post-dosage. Side-effects were mild and with small incidence. Metamizol is an effective, safe and low price drug. It may be regarded as a good alternative drug for the treatment of common acute primary headaches.

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