Migraine: a chronic sympathetic nervous system disorder

Headache. 2004 Jan;44(1):53-64. doi: 10.1111/j.1526-4610.2004.04011.x.


Objectives: To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine.

Background: Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy.

Methods: A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders.

Results: The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors.

Conclusions: The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Autonomic Nervous System Diseases / metabolism
  • Autonomic Nervous System Diseases / physiopathology*
  • Chronic Disease
  • Humans
  • Migraine Disorders / blood
  • Migraine Disorders / physiopathology*
  • Norepinephrine / blood
  • Norepinephrine / metabolism
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*


  • Norepinephrine