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2003 Wolff Award: Possible Parasympathetic Contributions to Peripheral and Central Sensitization During Migraine

Authors

  • David Yarnitsky MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • Itay Goor-Aryeh MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • Zahid H. Bajwa MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • Bernard I. Ransil PhD, MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • F. Michael Cutrer MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • Anna Sottile MD,

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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  • Rami Burstein PhD

    1. Departments of Anesthesia and Critical Care (Drs. Yarnitsky, Goor-Aryeh, Bajwa, Sottile, and Burstein) and Neurology (Drs. Yarnitsky, Bajwa, and Ransil), Beth Israel Deaconess Medical Center; the Department of Neurology, Massachusetts General Hospital (Dr. Cutrer); the Department of Neurobiology and the Program in Neuroscience, Harvard Medical School (Dr. Burstein), Boston, Mass. Dr. Yarnitsky's permanent address is the Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel.
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Address all correspondence to Dr. Rami Burstein, Department of Anesthesia and Critical Care, Harvard Institutes of Medicine, Room 830, 77 Avenue Louis Pasteur, Boston, MA 02115.

Abstract

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°C for cold, more than 45°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°C for cold, less than 40°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.

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