Current understanding of pineal gland structure and function in headache

Purpose The pineal gland plays an important role in biological rhythms, circadian and circannual variations, which are key aspects in several headache disorders. Overview Melatonin, the main pineal secreting hormone, has been extensively studied in primary and secondary headache disorders. Altered melatonin secretion occurs in many headache syndromes. Experimental data show pineal gland and melatonin both interfere in headache animal models, decreasing trigeminal activation. Melatonin has been shown to regulate CGRP and control its release. Discussion Melatonin has been used successfully as a treatment for migraine, cluster headaches and other headaches. There is a rationale for including the pineal gland as a relevant brain structure in the mechanisms of headache pathophysiology, and melatonin as a treatment option in primary headache.

Neurovascular mechanisms of migraine and cluster headache

Vascular theories of migraine and cluster headache have dominated for many years the pathobiological concept of these disorders. This view is supported by observations that trigeminal activation induces a vascular response and that several vasodilating molecules trigger acute attacks of migraine and cluster headache in susceptible individuals. Over the past 30 years, this rationale has been questioned as it became clear that the actions of some of these molecules, in particular, calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide, extend far beyond the vasoactive effects, as they possess the ability to modulate nociceptive neuronal activity in several key regions of the trigeminovascular system. These findings have shifted our understanding of these disorders to a primarily neuronal origin with the vascular manifestations being the consequence rather than the origin of trigeminal activation. Nevertheless, the neurovascular component, or coupling, seems to be far more complex than initially thought, being involved in several accompanying features. The review will discuss in detail the anatomical basis and the functional role of the neurovascular mechanisms relevant to migraine and cluster headache.

Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation

Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.