RES E A R C H A R T I C L E Open Access
Volume expansion of periaqueductal gray
in episodic migraine: a pilot MRI structural
, Xiaoyan Chen
, Mengqi Liu
, Shuangfeng Liu
, Lin Ma
and Shengyuan Yu
Background: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG
lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally
detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients
based on high resolution brain structural image.
Methods: The brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic
migraine (CM) on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template using
MRIcron, and the individual PAG was created by applying the deformation field to the PAG template after structural
image segment. One-way analysis of covariance, partial correlation analysis and Receiver operating characteristics
(ROC) curve were applied.
Results: EM had a larger PAG volume (0.35 ± 0.02 ml) than that (0.32 ± 0.02 ml) of NC (P = 0.017). The PAG volume of
CM (0.33 ± 0.02 ml) was negatively related to the VAS score (P = 0.03). ROC analysis demonstrated that PAG volume
has higher diagnostic efficacy (AUC, 0.731; Sensitivity, 0.556; Specificity, 0.889) for NC vs. EM compared with that NC vs.
CM (AUC, 0.634; Sensitivity, 0.438; Specificity, 0.833) and EM vs. CM (AUC, 0.618; Sensitivity, 0.813; Specificity, 0.556).
Conclusion: PAG volume expansion may be the direct impairment evidence on the brain in EM, and could be
considered as a diagnostic and evaluated imaging biomarker in migraine.
Keywords: Chronic migraine, Episodic migraine, Periaqueductal gray, Magnetic resonance imaging, Volume
The Migraine is a common type of primary headaches
with a reported prevalence of approximately 5.7% in
men and 17.0% in women , and affect 12% of the
population worldwide . The neuromechanism of
migraine has been the key focus of research . Of all
the target “generator” of migraine attacks, the PAG
region has been the key observed brain structure.
Periaqueductal gray (PAG) was a center with powerful
descending antinociceptive neuronal network in midbrain
[4, 5], and PAG activation was modulated by expectation
of pain  and placebo analgesia . PAG could exert a
dual control, including inhibition and facilitation, on noci-
ceptive transmission in the dorsal horn and trigeminal nu-
cleus  by descending PAG-RVM (rostral ventromedial
medulla) pathway contributing to central sensitization and
development of secondary hyperalgesia [8, 9]. A previous
study  confirmed PAG dysfunction in migraine, and
functional MRI studies demonstrated that the PAG dys-
function was associated with increased iron deposition,
which may play a role in the genesis or pathophysiology of
MOH [4, 11, 12] The PAG dysfunction changes might
explain the neuromechanism of migraine, however, the
PAG structure change was not elucidated completely.
PAG abnormalities can be detected in migraine
patients with brain T2-visible lesion using voxel-based
morphometry (VBM), which mainly identified increased
* Correspondence: email@example.com; firstname.lastname@example.org
Department of Radiology, Chinese PLA General Hospital, Fuxing Road 28,
Beijing 100853, China
Department of Neurology, Chinese PLA General Hospital, Fuxing Road 28,
Beijing 100853, China
Full list of author information is available at the end of the article
The Journal of Headache
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Chen et al. The Journal of Headache and Pain (2017) 18:83