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.

Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings

“…According to some research on migraine patients, inflammatory mediators may decrease the threshold for the onset of the attack, leading to central sensitization and promoting the persistence and progression of migraine [ 123 , 124 ]. As a result, a widespread alteration in inflammatory patterns is observed in migraine sufferers, supporting the hypothesis that inflammation plays a role in the evolution of the disease [ 125 , 126 , 127 , 128 , 129 ].…”

Immunologic aspects of migraine: A review of literature

“…Migraine headaches have also been claimed to be a neurological appearance of many autoimmune and immunological disorders which involve the central nervous system (CNS), such as multiple sclerosis (MS), or diseases with systematic aspects such as systemic lupus erythematosus (SLE) (2,(5)(6)(7)(8)(9)(10)(11).…”

Role of Peripheral Inflammatory Markers in Patients with Acute Headache Attack to Differentiate between Migraine and Non-Migraine Headache

“…A systemic pro-inflammatory status is the most robust experimental finding on migraines. However, it is still necessary to understand the extent to which the proinflammatory status of migraineurs reduces the threshold for trigeminovascular system activation, which is believed to promote neuroinflammatory events during migraine attacks [ 36 ]. Neuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder.…”

“…The potential relationship between platelet biology and headache, particularly migraine, has been studied for many years. Despite clinical evidence that patients with essential thrombocythemia have a high frequency of headache, epidemiological studies that have investigated the platelet count in patients with migraine failed to find significant associations [ 36 ]. In addition, a possible link between platelet biology and migraine is represented by inflammation.…”