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Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging.
Cephalalgia 2019; 39(11):1407-1420C

Abstract

BACKGROUND

Initiating mechanisms of migraine headache remain poorly understood and a biomarker of migraine does not exist. Inflammation pertaining to the wall of cerebral arteries and brain parenchyma has been suggested to play a role in migraine pathophysiology.

OBJECTIVE

We conducted the first experimental human study to investigate macrophage-mediated inflammation as a possible biomarker of migraine.

METHODS

Using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced 3T magnetic resonance imaging (MRI), we investigated the presence of macrophages in cerebral artery walls and in brain parenchyma of patients with migraine without aura. We used the phosphodiesterase-3-inhibitor cilostazol as an experimental migraine trigger, and investigated both patients who received sumatriptan treatment, and patients who did not. To validate our use of USPIO-enhanced MRI, we included a preclinical mouse model with subcutaneous capsaicin injection in the trigeminal V1 area. The study is registered at ClinicalTrials.gov with the identifier NCT02549898.

RESULTS

A total of 28 female patients with migraine without aura underwent a baseline MRI scan, ingested cilostazol, developed a migraine-like attack, and underwent an USPIO-enhanced MRI scan > 24 hours after intravenous administration of USPIO. Twelve patients treated their attack with 6 mg s.c. sumatriptan, while the remaining 16 patients received no migraine-specific rescue medication. The preclinical model confirmed that USPIO-enhanced MRI detects macrophage-mediated inflammation. In patients, however, migraine attacks were not associated with increased USPIO signal on the pain side of the head compared to the non-pain side.

CONCLUSION

Our findings suggest that migraine without aura is not associated with macrophage-mediated inflammation specific to the head pain side.

Authors+Show Affiliations

Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.Cluster for Molecular Imaging, Department of Biomedical Research and Department of Clinical Physiology, Nuclear Medicine & PET, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.Department of Radiology, Rigshospitalet Glostrup, Copenhagen, Denmark.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.Department of Hematology, Herlev Hospital, Herlev, Denmark.Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.Cluster for Molecular Imaging, Department of Biomedical Research and Department of Clinical Physiology, Nuclear Medicine & PET, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark.Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, Copenhagen, Denmark.Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, Copenhagen, Denmark.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31104505

Citation

Khan, Sabrina, et al. "Investigating Macrophage-mediated Inflammation in Migraine Using Ultrasmall Superparamagnetic Iron Oxide-enhanced 3T Magnetic Resonance Imaging." Cephalalgia : an International Journal of Headache, vol. 39, no. 11, 2019, pp. 1407-1420.
Khan S, Amin FM, Fliedner FP, et al. Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging. Cephalalgia. 2019;39(11):1407-1420.
Khan, S., Amin, F. M., Fliedner, F. P., Christensen, C. E., Tolnai, D., Younis, S., ... Ashina, M. (2019). Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging. Cephalalgia : an International Journal of Headache, 39(11), pp. 1407-1420. doi:10.1177/0333102419848122.
Khan S, et al. Investigating Macrophage-mediated Inflammation in Migraine Using Ultrasmall Superparamagnetic Iron Oxide-enhanced 3T Magnetic Resonance Imaging. Cephalalgia. 2019;39(11):1407-1420. PubMed PMID: 31104505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging. AU - Khan,Sabrina, AU - Amin,Faisal Mohammad, AU - Fliedner,Frederikke Petrine, AU - Christensen,Casper Emil, AU - Tolnai,Daniel, AU - Younis,Samaira, AU - Olinger,Anne Christine Rye, AU - Birgens,Henrik, AU - Daldrup-Link,Heike, AU - Kjær,Andreas, AU - Larsson,Henrik Bo Wiberg, AU - Lindberg,Ulrich, AU - Ashina,Messoud, Y1 - 2019/05/19/ PY - 2019/5/21/pubmed PY - 2019/5/21/medline PY - 2019/5/21/entrez KW - Headache KW - USPIO KW - dura mater KW - ferumoxytol KW - inflammation KW - meningeal nociceptor SP - 1407 EP - 1420 JF - Cephalalgia : an international journal of headache JO - Cephalalgia VL - 39 IS - 11 N2 - BACKGROUND: Initiating mechanisms of migraine headache remain poorly understood and a biomarker of migraine does not exist. Inflammation pertaining to the wall of cerebral arteries and brain parenchyma has been suggested to play a role in migraine pathophysiology. OBJECTIVE: We conducted the first experimental human study to investigate macrophage-mediated inflammation as a possible biomarker of migraine. METHODS: Using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced 3T magnetic resonance imaging (MRI), we investigated the presence of macrophages in cerebral artery walls and in brain parenchyma of patients with migraine without aura. We used the phosphodiesterase-3-inhibitor cilostazol as an experimental migraine trigger, and investigated both patients who received sumatriptan treatment, and patients who did not. To validate our use of USPIO-enhanced MRI, we included a preclinical mouse model with subcutaneous capsaicin injection in the trigeminal V1 area. The study is registered at ClinicalTrials.gov with the identifier NCT02549898. RESULTS: A total of 28 female patients with migraine without aura underwent a baseline MRI scan, ingested cilostazol, developed a migraine-like attack, and underwent an USPIO-enhanced MRI scan > 24 hours after intravenous administration of USPIO. Twelve patients treated their attack with 6 mg s.c. sumatriptan, while the remaining 16 patients received no migraine-specific rescue medication. The preclinical model confirmed that USPIO-enhanced MRI detects macrophage-mediated inflammation. In patients, however, migraine attacks were not associated with increased USPIO signal on the pain side of the head compared to the non-pain side. CONCLUSION: Our findings suggest that migraine without aura is not associated with macrophage-mediated inflammation specific to the head pain side. SN - 1468-2982 UR - https://www.unboundmedicine.com/medline/citation/31104505/Investigating_macrophage-mediated_inflammation_in_migraine_using_ultrasmall_superparamagnetic_iron_oxide-enhanced_3T_magnetic_resonance_imaging L2 - http://journals.sagepub.com/doi/full/10.1177/0333102419848122?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -