Update on the pathophysiology of cluster headache: Imaging and neuropeptide studies

Journal article

Buture, A., Boland, J. W., Dikomitis, L. and Ahmed, F. 2022. Update on the pathophysiology of cluster headache: Imaging and neuropeptide studies. Journal of Pain Research. 12, pp. 269-281. https://doi.org/10.2147/JPR.S175312
AuthorsButure, A., Boland, J. W., Dikomitis, L. and Ahmed, F.
Abstract

Objective
Cluster headache (CH) is the most severe primary headache condition. Its pathophysiology is multifaceted and incompletely understood. This review brings together the latest neuroimaging and neuropeptide evidence on the pathophysiology of CH.

Methods
A review of the literature was conducted by searching PubMed and Web of Science. The search was conducted using the following keywords: imaging studies, voxel-based morphometry, diffusion-tensor imaging, diffusion magnetic resonance imaging, tractography, connectivity, cerebral networks, neuromodulation, central modulation, deep brain stimulation, orexin-A, orexin-B, tract-based spatial statistics, single-photon emission computer tomography studies, positron-emission tomography, functional magnetic resonance imaging, magnetic resonance spectroscopy, trigeminovascular system, neuropeptides, calcitonin gene-related peptide, neurokinin A, substance P, nitric oxide synthase, pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, neuropeptide Y, acetylcholine, noradrenaline, and ATP. “Cluster headache” was combined with each keyword for more relevant results. All irrelevant and duplicated records were excluded. Search dates were from October 1976 to May 2018.

Results
Neuroimaging studies support the role of the hypothalamus in CH, as well as other brain areas involved in the pain matrix. Activation of the trigeminovascular system and the release of neuropeptides play an important role in CH pathophysiology. Among neuropeptides, calcitonin gene-related peptide, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide have been reported to be reliable biomarkers for CH attacks, though not specific for CH. Several other neuropeptides are involved in trigeminovascular activation, but the current evidence does not qualify them as reliable biomarkers in CH.

Conclusion
CH has a complex pathophysiology and the pain mechanism is not completely understood. Recent neuroimaging studies have provided insight into the functional and structural network bases of CH pathophysiology. Although there has been important progress in neuropeptide studies, a specific biomarker for CH is yet to be found.

KeywordsVoxel-based morophomertry; Single-photon emission computer tomography; Positron-emission tomography; Functional magnetic resonance imaging; Calcitonin gene-related peptide; Pituitary adenylate cyclase-activating peptide
Year2022
JournalJournal of Pain Research
Journal citation12, pp. 269-281
PublisherTaylor & Francis
Dove Press
ISSN1178-7090
Digital Object Identifier (DOI)https://doi.org/10.2147/JPR.S175312
Official URLhttps://www.tandfonline.com/doi/full/10.2147/JPR.S175312
Publication process dates
Deposited27 Jun 2023
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Chris Littlewood, Marcus Bateman, Kendra Cooke, Susie Hennnings, Tina Cookson, Kieran Bromley, Martyn Lewis, Lennard Funk, Jean Denton, Maria Moffatt, Rachel Winstanley, Saurabh Mehta, Gareth Stephens, Lisa Dikomitis, Linda Chesterton and Nadine E. Foster 2019. Protocol for a multi-centre pilot and feasibility randomised controlled trial with a nested qualitative study: rehabilitation following rotator cuff repair (the RaCeR study). Trials. 20 (328). https://doi.org/10.1186/s13063-019-3407-3
Exploring differences in individual and group judgements in standard setting
Peter Yeates, Natalie Cope, Eva Luksaite, Andrew Hassell and Lisa Dikomitis 2019. Exploring differences in individual and group judgements in standard setting. Medical Education. 53 (9), pp. 941-962. https://doi.org/10.1111/medu.13915
Images depicting headache pain – a tool to aid the diagnosis of cluster headache: a pilot study
Dikomitis, L. 2019. Images depicting headache pain – a tool to aid the diagnosis of cluster headache: a pilot study. Journal of Multidisciplinary Healthcare. 2019 (12), pp. 691-698. https://doi.org/10.2147/JMDH.S207128
Images depicting pain: a screening tool for cluster headache
Buture, A., Dikomitis, L., Boland, L. and Ahmed, F. 2018. Images depicting pain: a screening tool for cluster headache. Cephalalgia. 38 (Supp 1), pp. 114-115. https://doi.org/10.1177/0333102418789865
Delays in the diagnosis and misdiagnosis of cluster headache – a systematic literature review
Buture, A., Boland, J. W., Dikomitis, L. and Ahmed, F. 2018. Delays in the diagnosis and misdiagnosis of cluster headache – a systematic literature review. Cephalalgia. 38 (Supp 1), pp. MTIS2018-145.
Systematic literature review on the delays in the diagnosis and misdiagnosis of cluster headache
Buture, A., Boland, J. W., Dikomitis, L. and Ahmed, F. 2018. Systematic literature review on the delays in the diagnosis and misdiagnosis of cluster headache. Neurological Sciences. 40, pp. 25-39. https://doi.org/10.1007/s10072-018-3598-5
Visual images: an additional tool for the screening of cluster headache
Buture, A., Dikomitis, L., Boland, J. W. and Ahmed, F. 2017. Visual images: an additional tool for the screening of cluster headache. Cephalalgia. 37, p. 219.
So looking at this, you look like you've got some issues going on with your joints: Exploring case-finding in long-tern condition review consultations - the ENHANCE pilot trial
Liddle, J., Chew-Graham, C. A., Mallen, C. D., Healey, E. L., Jinks, C. and Dikomitis, L. 2017. So looking at this, you look like you've got some issues going on with your joints: Exploring case-finding in long-tern condition review consultations - the ENHANCE pilot trial. Rheumatology. 56 (IS 2). https://doi.org/10.1093/rheumatology/kex062.181
'"The man who closed the asylums": Franco Basaglia and the revolution in mental health care', by John Foot (Verso, 2015)
Dikomitis, L. 2016. '"The man who closed the asylums": Franco Basaglia and the revolution in mental health care', by John Foot (Verso, 2015). Durham University Institute for Medical Humanities.
How do clinicians think about cluster headache
Dikomitis, L., Paemeleire, K., Goadsby, P. J. and Ahmed, F. 2016. How do clinicians think about cluster headache. Cephalalgia. 36 (S 1).
Developing a diagnostic tool for the early diagnosis of cluster headache
Buture, A., Dikomitis, L. and Ahmed, F. 2016. Developing a diagnostic tool for the early diagnosis of cluster headache. Cephalalgia.
Perceptions, understandings and experiences of cluster headache patients in the north of England: a qualitative study
Dikomitis, L., Quarshie, V., Paemeleire, K., Goadsby, P. J. and Ahmed, F. 2015. Perceptions, understandings and experiences of cluster headache patients in the north of England: a qualitative study. Cephalalgia. 25 (S6).
[Review of] The Past in Pieces: Belonging in the New Cyprus, by Rebecca Bryant. Contemporary Ethnography series. Philadelphia: University of Pennsylvania Press, 2010. 224 pp.
Dikomitis, L. 2014. [Review of] The Past in Pieces: Belonging in the New Cyprus, by Rebecca Bryant. Contemporary Ethnography series. Philadelphia: University of Pennsylvania Press, 2010. 224 pp. American Anthropologist. 116 (1), pp. 194-195. https://doi.org/10.1111/aman.12085_9
Perceptions and experiences of cluster headache among patients, general practitioners and neurologists in the north of england: A qualitative study
Ahmed, F., Dikomitis, L., Zafar, H. W., Goadsby, P. and Paemeliere, P. 2014. Perceptions and experiences of cluster headache among patients, general practitioners and neurologists in the north of england: A qualitative study. Journal of Headache and Pain. 15 (S1).
Patients perceptions of the causes of migraine in Flanders (Belgium): A qualitative study
Dikomitis, L., Bonte, M., Willems, S. and Paemeleire, K. 2013. Patients perceptions of the causes of migraine in Flanders (Belgium): A qualitative study. Cephalalgia. 33 (S 8), p. 198. https://doi.org/10.1177/0333102413490487