Skip to main content

EHMTI-0149. Low CSF hypocretin-1 levels are associated with cluster headache


Cluster headache (CH) is a debilitating headache disorder with strong chronobiological features characterized by severe pain attacks often waking the patient from sleep. Hypocretin (HCRT) is involved in the regulation of arousal and pain and is produced in the hypothalamus. HCRT has been suggested to play a role in the pathology of CH.


To investigate HCRT-1 levels in CH during active bout.


CSF HCRT was measured in 12 chronic and 14 episodic CH patients during active bout, and in 27 healthy controls. Patients were characterized beyond the dichotomy of current diagnostic criteria (episodic/chronic) using a CH index reflecting total headache duration and their attack rhythmicity compared to HCRT concentrations.


We found lower HCRT-1 levels in both chronic (388.67 pg/ml, p=0.0221) and episodic cluster headache (375.36 pg/ml, p=0.0005) compared with controls (430.96 pg/ml) and a tendency towards relatively higher values in chronic CH compared with episodic CH. A positive relationship between the CH index and HCRT concentrations was found in all patients (R2=0.1541, p=0.0473). We also identified a tendency towards relatively higher HCRT concentrations in patients without chronological rhythmicity.


This is the first report of lower HCRT-1 concentrations in CH suggesting that decreased levels may reflect an insufficient anti-nociceptive activity of the hypothalamus. The exact mechanism of the anti-nociceptive effect of HCRT is not known and requires further investigation. In conclusion, this study supports the hypothesis of a connection between arousal- and pain- regulation and the pathogenesis of CH.

No conflict of interest.

Author information



Corresponding author

Correspondence to M Barloese.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Barloese, M., Jennum, P., Lund, N. et al. EHMTI-0149. Low CSF hypocretin-1 levels are associated with cluster headache. J Headache Pain 15, E14 (2014).

Download citation


  • Cluster Headache
  • Headache Disorder
  • Chronic Cluster Headache
  • Cluster Headache Patient
  • Current Diagnostic Criterion