Exaggerated parasympathetic pupillary response in individuals with migraine during interictal phase from application of the cold pressor test suggests a disbalance of the cranial autonomic nervous system (ANS), demonstrating that brainstem parasympathetic dysregulation may have a significant role in migraine pathophysiology, according to a prospective observational study published in BMC Neurology.

The study included 20 participants in the migraine group and 20 in the control group. Individuals selected for the migraine group had a diagnosis of episodic migraine and no history of autonomic dysfunction. Patients in the control group only had a history of occasional headaches. Members of both groups underwent a cold pressor test, where they dipped their left hand into ice-cold water for no more than 5 minutes. Infrared monocular pupillometry was applied at baseline, 2 minutes, and 5 minutes to measure light reflex parameters and pupil diameter.

Results showed no significant differences until the 5-minute time, when pupillary light reflex constriction velocity measured significantly higher for subjects in the migraine group than those in the control group (5.59 ± 0.73 mm/s vs 5.16 ± 0.53 mm/s; unpaired t-test P<.05). This suggests an exaggerated parasympathetic response of the cranial ANS in patients with interictal migraine, though the study was not without limitations. The study aimed to assess the cranial ANS in individuals with migraine by using the cold pressor test; it did not analyze the power spectrum of heart rate variability, instead focusing on the cranial ANS response during the testing.

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Although further research should be conducted to determine the role of upper brainstem parasympathetic dysregulation in the pathophysiology of migraine, the results of sympathetic stimulation in this study indicate different activation thresholds of the cranial ANS in individuals with interictal migraine.


Eren OE, Ruscheweyh R, Schankin C, Schöberl F, Straube A. The cold pressor test in interictal migraine patients – different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous systemBMC Neurol. 2018;18(1).