The Hypothalamic Orexinergic System: Pain and Primary Headaches



  • Philip Holland PhD,

  • Peter J. Goadsby MD, PhD

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  • From Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK (Drs. Holland and Goadsby); Department of Neurology, University of California, San Francisco, San Francisco CA, USA (Dr. Goadsby).

Address all correspondence to Dr. Peter J. Goadsby, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.


The primary headaches are a group of distinct individually characterized attack forms, which although varying in presentation, share some common anatomical basis responsible for the pain component of the attack. The hypothalamus is known to modulate a multitude of functions and has been shown to be involved in the pathophysiology of a variety of primary headaches including cluster headache and chronic migraine. It seems likely that it may be involved in other primary headache disorders due to their episodic nature and may underlie many of their diverse symptoms. We discuss the hypothalamic involvement in the modulation of trigeminovascular processing and examine the involvement of the hypothalamic orexinergic system as a key regulator of this function.