Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding

Marie Deen; Anders Hougaard; Hanne D. Hansen; Claus Svarer; Hans Eiberg; Szabolcs Lehel; Gitte M. Knudsen; Messoud Ashina

doi:10.1177/0333102418793642

Migraine is associated with high brain 5-HT levels as indexed by 5-HT₄ receptor binding

Marie Deen, Anders Hougaard, Hanne D. Hansen, Claus Svarer, Hans Eiberg, Szabolcs Lehel, Gitte M. Knudsen, Messoud Ashina^*

^*Corresponding author for this work

4 Citations (Scopus)

Abstract

Introduction: Serotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT₄ receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency. Methods: Sixteen chronic migraine patients underwent a dynamic PET scan after injection of [¹¹C]SB207145, a specific 5-HT₄ receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT₄ receptor binding was used as a proxy for brain 5-HT levels, since 5-HT₄ receptor binding is inversely related to brain 5-HT levels. Results: Chronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT₄ receptor binding compared to controls (p = 0.039). There was no difference in 5-HT₄ receptor binding between chronic and episodic migraine patients (p = 0.48) and no association between number of monthly migraine days and 5-HT₄ receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39). Conclusion: The finding of low 5-HT₄ receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.

Original language	English
Journal	Cephalalgia
ISSN	0333-1024
DOIs	https://doi.org/10.1177/0333102418793642
Publication status	Published - 1 Apr 2019

Keywords

chronic migraine
CNS
Headache
neuroimaging
pain
PET

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10.1177/0333102418793642

Cite this

@article{4c685986f6554930ab90fadd8244b79b,

title = "Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding",

abstract = "Introduction: Serotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT4 receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency. Methods: Sixteen chronic migraine patients underwent a dynamic PET scan after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT4 receptor binding was used as a proxy for brain 5-HT levels, since 5-HT4 receptor binding is inversely related to brain 5-HT levels. Results: Chronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT4 receptor binding compared to controls (p = 0.039). There was no difference in 5-HT4 receptor binding between chronic and episodic migraine patients (p = 0.48) and no association between number of monthly migraine days and 5-HT4 receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39). Conclusion: The finding of low 5-HT4 receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.",

keywords = "chronic migraine, CNS, Headache, neuroimaging, pain, PET",

author = "Marie Deen and Anders Hougaard and Hansen, {Hanne D.} and Claus Svarer and Hans Eiberg and Szabolcs Lehel and Knudsen, {Gitte M.} and Messoud Ashina",

year = "2019",

month = apr,

day = "1",

doi = "10.1177/0333102418793642",

language = "English",

journal = "Cephalalgia, Supplement",

issn = "0800-1952",

publisher = "SAGE Publications",

}

TY - JOUR

T1 - Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding

AU - Deen, Marie

AU - Hougaard, Anders

AU - Hansen, Hanne D.

AU - Svarer, Claus

AU - Eiberg, Hans

AU - Lehel, Szabolcs

AU - Knudsen, Gitte M.

AU - Ashina, Messoud

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Introduction: Serotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT4 receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency. Methods: Sixteen chronic migraine patients underwent a dynamic PET scan after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT4 receptor binding was used as a proxy for brain 5-HT levels, since 5-HT4 receptor binding is inversely related to brain 5-HT levels. Results: Chronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT4 receptor binding compared to controls (p = 0.039). There was no difference in 5-HT4 receptor binding between chronic and episodic migraine patients (p = 0.48) and no association between number of monthly migraine days and 5-HT4 receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39). Conclusion: The finding of low 5-HT4 receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.

AB - Introduction: Serotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT4 receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency. Methods: Sixteen chronic migraine patients underwent a dynamic PET scan after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT4 receptor binding was used as a proxy for brain 5-HT levels, since 5-HT4 receptor binding is inversely related to brain 5-HT levels. Results: Chronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT4 receptor binding compared to controls (p = 0.039). There was no difference in 5-HT4 receptor binding between chronic and episodic migraine patients (p = 0.48) and no association between number of monthly migraine days and 5-HT4 receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39). Conclusion: The finding of low 5-HT4 receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.

KW - chronic migraine

KW - CNS

KW - Headache

KW - neuroimaging

KW - pain

KW - PET

U2 - 10.1177/0333102418793642

DO - 10.1177/0333102418793642

M3 - Journal article

C2 - 30089402

AN - SCOPUS:85052560320

SN - 0800-1952

JO - Cephalalgia, Supplement

JF - Cephalalgia, Supplement

ER -