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Updated: Jun 25, 2026

Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
Published on: August 4, 2023
Cluster headache, hypothalamus, and orexin
Philip R Holland1, Peter J Goadsby
1Headache Research Group, Department of Neurology, University of California, San Francisco, Box 0114, 505 Parnassus Avenue, San Francisco, CA 94143, USA. philip.holland@headache.ucsf.edu
Abstract:
Cluster headache (CH) is a highly disabling condition resulting in severe, recurrent unilateral bouts of pain and accompanying autonomic symptoms. This review describes some current views regarding the underlying pathophysiology covering the pain and cranial autonomic (parasympathetic) activation, and highlights the potential importance of the hypothalamus in CH. The hypothalamus is known to modulate many functions and has been shown to be involved in the pathophysiology of a variety of primary headaches, including CH. Hypothalamic structures are likely to underlie the circadian and circannual periodicity of attacks and contribute to the pain and autonomic disturbances. We discuss the hypothalamic involvement in CH and modulation of trigeminovascular processing and examine the emerging involvement of the hypothalamic orexinergic system as a possible key pathway in CH pathophysiology.
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