Central 5-Ht Receptor Hypersensitivity in Migraine Without Aura

Abstract

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.

Anger, Depression and Personality Dimensions in Patients with Migraine without Aura

“…In other words, the coexistence of these elements is not accidental; rather, it is rooted in some common patterns of neurobiological functioning. Depressed [50] and migraine patients [59] as well as angry subjects [60, 61 share a similarly disordered serotonin system].…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Further lines of evidence support the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT 1A receptors. This is of relevance given the role of the 5-HT 1A receptor in controlling raphe 5-HT neuronal tone and the possible association between migraine, anxiety, and depression (Cassidy et al 2003). Furthermore, most antimigraine drugs display high affinity for 5-HT 1A and/or 5-HT 2 receptor subtypes in human brain (Peroutka 1988).…”

Interictal Brain 5-HT1A Receptors Binding in Migraine Without Aura: A 18F-MPPF-PET Study

“…Similarly, the preventive treatments methysergide and pizotifen, antagonists of 5-HT2 receptors, also have a weak affinity for 5-HT1A receptors (6,7); in consequence, 5-HT1A receptors may also contribute to the efficacy of some drugs used in migraine prophylaxis (9). 5-HT1A receptor hypersensitivity is the most likely explanation for the increased prolactine response to buspirone, a 5-HT1A receptor agonist, in migrainous patients (10). Finally, an increase of serotonin synthesis during migraine attacks has been demonstrated in vivo in patients suffering from migraine without aura doi: 10.1111/j.1468-2982.2008.01677.x using positron emission tomography (PET) and a-[ 11 C]methyl-L-tryptophan (AMT) (11) and could reflect an alteration of 5-HT synthesis via regulation of 5-HT1A raphe autoreceptors.…”