Studies of lipolysis and neuroendocrine rhythms in cluster headache

Abstract

Cluster headache (CH) is characterised by excruciating, unilateral headache attacks, which in the episodic form appear in clusters for weeks or even months. The headache attacks are often accompanied by ipsilateral, cranial autonomic symptoms supporting a local peripheral sympathetic deficit and a parasympathetic discharge. CH attacks are also associated with various cardiovascular changes indicating a systemic, autonomic disturbance as well, although the reports are contradictory.

The etiology of CH is not known but a hypothalamic involvement is strongly suggested. Since hypothalamus is of great importance for the integration of autonomic nervous system signals, a disturbance in this area provides a possibility of a systemic, autonomic dysfunction of central origin in CH. The overall objective with this project was to focus on a better understanding of autonomic and neuroendocrine functions in CH. As a metabolic marker of systemic autonomic activity, adipose tissue lipolysis was studied, a metabolic function that is directly and indirectly regulated by hypothalamus.

In study I we investigated nocturnal lipolysis in CH patients as a marker for nocturnal sympathetic function compared to healthy controls. We found diminished nocturnal lipolysis in CH patients, both in active period and in remission. In addition, patients in remission showed an altered nocturnal lipolysis rhythm. These findings reflect for the first time a metabolic disturbance in CH and may be a result of a systemic sympathetic dysregulation, possibly at a hypothalamic level. Most of the CH patients are heavy smokers.

In study II we investigated to which extent smoking habits affect lipolysis in habitual smokers. We did not find any differences in nocturnal lipolysis between healthy smokers, after short-term nicotine withdrawal, and healthy non-smokers, which indicates that our finding of diminished nocturnal lipolysis in CH patients is not explained by smoking habits. The lipolytic activity may be affected by disturbed ß-receptor function.

In study III we showed that diminished lipolysis in CH is not caused by defective ß-receptors in adipose tissue, at least not in remission. On the contrary, ß-receptors in adipose tissue appeared to be up-regulated, which may be a sign of decreased sympathetic tone and in support of a systemic sympathetic dysregulation in CH.

In study IV we investigated if a diminished lipolysis in CH remission could be a result of altered nocturnal secretion of noradrenaline, growth hormone (GH), insulin or cortisol, hormones with a potential effect on lipolysis and which at least partly are regulated by hypothalamic activity. We found lower GH concentrations during the early part of the night in CH but a normal secretion of noradrenaline, insulin and cortisol compard to controls. We suggested that the altered nocturnal GH pattern in remission in part may explain the altered nocturnal lipolysis in CH and support a permanent hypothalamic disturbance in CH.