Brain-derived neurotrophic factor in primary headaches

Abstract

Brain derived neurotrophic factor (BDNF) is associated with pain modulation and central sensitization. Recently, a role of BDNF in migraine and cluster headache pathophysiology has been suspected due to its known interaction with calcitonin gene-related peptide. Bi-center prospective study was done enrolling four diagnostic groups: episodic migraine with and without aura, episodic cluster headache, frequent episodic tension-type headache, and healthy individuals. In migraineurs, venous blood samples were collected twice: outside and during migraine attacks prior to pain medication. In cluster headache patients serum samples were collected in and outside cluster bout. Analysis of BDNF was performed using enzyme-linked immunosorbent assay technique. Migraine patients revealed significantly higher BDNF serum levels during migraine attacks (n = 25) compared with headache-free intervals (n = 53, P < 0.01), patients with tension-type headache (n = 6, P < 0.05), and healthy controls (n = 22, P < 0.001). There was no significant difference between patients with migraine with aura compared with those without aura, neither during migraine attacks nor during headache-free periods. Cluster headache patients showed significantly higher BDNF concentrations inside (n = 42) and outside cluster bouts (n = 24) compared with healthy controls (P < 0.01, P < 0.05). BDNF is increased during migraine attacks, and in cluster headache, further supporting the involvement of BDNF in the pathophysiology of these primary headaches.

Neurotrophic factors in tension-type headache

“…This finding is in line with a previous study showing that BDNF serum levels in TTH patients were not different from control subjects 6 . This previous study included only 6 patients with ETTH without pain at the time of evaluation and 22 healthy controls.…”

“…In other primary headache disorders, such as migraine and cluster headache, the levels of NF were registered to be higher during pain attacks 6,7 . It is possible that this is not the case for TTH.…”

“…A recent study showed that patients with frequent ETTH had not significant different BDNF levels as compared with controls 6 . No previous study has investigated differences in NF between ETTH and CTTH.…”

“…Reduced BDNF and NGF platelet levels have been described in patients with migraine and chronic daily headache (CDH) 5 . BDNF was shown to be increased during migraine and cluster headache attacks 6,7 . Increased cerebrospinal fluid (CSF) levels of NGF and BDNF, …”

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

“…Some studies have proposed that pro-and anti-inflammatory molecules may play a role in the pathophysiology of migraine 8,9,10 and TTH 11,12,13 . The association between neurotrophic factors and migraine 14,15,16 , and neurotrophic factors and TTH 17,18 has also been investigated. As different pathophysiological mechanisms have been proposed for migraine and TTH, it is possible that the profile of these molecules may be distinct in these two disorders.…”