{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:16:55Z","timestamp":1772579815068,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85\u2009years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high\u2010field (7 Tesla) and high\u2010resolution functional magnetic resonance imaging (MRI) at each visit.<\/jats:p>\n                    <jats:p>Functional connectivity was assessed at the two visits by performing a region\u2010of\u2010interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region\u2010of\u2010interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A\u2010delta\u2010mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T\u2009=\u2009\u221240.79).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A\u2010delta\u2010mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14752","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T06:37:43Z","timestamp":1719211063000},"page":"729-737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circadian functional changes of pain\u2010processing brainstem nuclei and implications for cluster headache: A 7 Tesla imaging study"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2778-6790","authenticated-orcid":false,"given":"Heiko","family":"Pohl","sequence":"first","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6410-5547","authenticated-orcid":false,"given":"Maria S.","family":"Neumeier","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-0200","authenticated-orcid":false,"given":"Andreas R.","family":"Gantenbein","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"},{"name":"Department of Neurology and Neurorehabilitation ZURZACH Care  Bad Zurzach Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Wegener","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"},{"name":"Department of Neurology University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Rosio","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Clinical Neuroscience Center University Hospital Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franciszek","family":"Hennel","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering ETH Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-5555","authenticated-orcid":false,"given":"Peter S.","family":"Sandor","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"},{"name":"Department of Neurology and Neurorehabilitation ZURZACH Care  Bad Zurzach Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1748-174X","authenticated-orcid":false,"given":"Michael","family":"Weller","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich, Clinical Neuroscience Centre  Zurich Switzerland"},{"name":"Department of Neurology University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-1100","authenticated-orcid":false,"given":"Lars","family":"Michels","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Clinical Neuroscience Center University Hospital Zurich  Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich and Swiss Federal Institute of Technology Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"e2224","DOI":"10.1212\/WNL.0000000000207240","article-title":"Circadian features of cluster headache and migraine: a systematic review, meta\u2010analysis, and genetic analysis","volume":"100","author":"Benkli B","year":"2023","journal-title":"Neurology"},{"key":"e_1_2_12_3_1","first-page":"5","article-title":"Cluster headache pathophysiology\u2014a disorder of network excitability? 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