Migraine: A Chronic Sympathetic Nervous System Disorder

Stephen J. Peroutka


Headache. 2004;44(1) 

In This Article


Norepinephrine is a major sympathetic neurotransmitter, and it acts on both α- and β-adrenergic receptors. The sensitivity of these adrenergic receptors to various pharmacological agents can be tested objectively. A dose response can be defined using α-adrenergic agonists to increase blood pressure (BP). Both the pharmacological dose needed to significantly increase BP and the degree of BP increase at a given dose are quantitative measures of α-adrenergic receptor sensitivity.

In Individuals with Pure Autonomic Failure and Multiple System Atrophy. In individuals with PAF, the dose response curve to NE is shifted significantly to the left, indicating enhanced α-adrenergic receptor sensitivity. A less extreme adrenergic receptor supersensitivity is observed in patients with MSA because their dose response curve to NE is not shifted to the left. The magnitude of BP increase to a given dose of NE, however, is enhanced compared to controls, although not as high as is observed in patients with PAF.[3]

In Migraineurs. Adrenergic receptor supersensitivity has also been observed in migraineurs in response to the pharmacological effects of NE. The length of time that the BP is significantly elevated after a bolus injection of 0.1 µg/kg NE is significantly longer (P< .001) in migraineurs with aura (101 seconds) and without aura (91 seconds) than in controls (21 seconds).[7]

Alpha-adrenergic receptor supersensitivity has also been demonstrated in migraineurs by injecting the α-adrenergic agonist, phenylephrine. The pressor response to an intravenous injection of 100 µg phenylephrine was significantly greater, as well as more prolonged, in migraineurs versus controls.[13] Phenylephrine increased systolic and diastolic BPs, the mean arterial pressures, and heart rate significantly more in migraineurs versus controls.[13] The BP response to phenylephrine is even more significant in migraineurs with a history of syncope, suggesting that these individuals have a more severe sympathetic deficiency with secondary adrenergic hypersensitivity than migraineurs without syncope.[14]


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