2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine

Headache. 2003 Jul-Aug;43(7):704-14. doi: 10.1046/j.1526-4610.2003.03127.x.


Background: Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nociceptors. We recently showed that activation of intracranial perivascular nociceptors induces peripheral and central sensitization along the trigeminovascular pathway and proposed that these sensitizations mediate the intracranial hypersensitivity and the cutaneous allodynia of migraine.

Methods: The present study investigates possible parasympathetic contributions to the generation of peripheral and central sensitization during migraine by applying intranasal lidocaine to reduce cranial parasympathetic outflow through the sphenopalatine ganglion.

Results: In the absence of migraine, patients were pain-free, and their skin sensitivity was normal. Their mean baseline pain thresholds were less than 15 degrees C for cold, more than 45 degrees C for heat, and more than 100 g for mechanical pressure. Their mean pain score was 7.5 of 10 (standard deviation, 1.4) during untreated migraine and 3.5 of 10 (standard deviation, 2.4) after the nasal lidocaine-induced sphenopalatine ganglion block (P <.0001). Most patients developed cutaneous allodynia during migraine, and their mean pain thresholds changed to more than 25 degrees C for cold, less than 40 degrees C for heat, and less than 10 g for mechanical pressure. Following the nasal lidocaine administration (sphenopalatine ganglion block), this allodynia remained unchanged in spite of the pain relief.

Conclusion: These findings suggest that cranial parasympathetic outflow contributes to migraine pain by activating or sensitizing (or both) intracranial nociceptors, and that these events induce parasympathetically independent allodynia by sensitizing the central nociceptive neurons in the spinal trigeminal nucleus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intranasal
  • Adult
  • Aged
  • Awards and Prizes*
  • Central Nervous System / physiopathology*
  • Female
  • Humans
  • Lidocaine / administration & dosage
  • Male
  • Middle Aged
  • Migraine Disorders / classification
  • Migraine Disorders / physiopathology*
  • Nerve Block
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain Threshold / drug effects
  • Parasympathetic Nervous System / physiopathology*
  • Peripheral Nervous System / physiopathology*
  • Random Allocation
  • Skin / physiopathology


  • Lidocaine