{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:49:14Z","timestamp":1784101754588,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005747","name":"A.P. M\u00f8ller og Hustru Chastine Mc-Kinney M\u00f8llers Fond til almene Formaal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009997","name":"International Headache Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009997","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["276\u20102018\u2010403"],"award-info":[{"award-number":["276\u20102018\u2010403"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Caffeine, a non\u2010selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female Sprague\u2013Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120\u2009mg\/kg intraperitoneally) was given. In a second group (non\u2010implanted), the acute effects of 30\u2009mg\/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross\u2010over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A single dose of 30\u2009mg\/kg caffeine lowered the ICP by 35% at 165\u2009min after administration (saline: 0.16\u2009\u00b1\u20090.9 vs caffeine: \u22121.18\u2009\u00b1\u20090.9 \u0394mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0098) and lasted up to 12\u2009h. Administration of 120\u2009mg\/kg caffeine showed a faster onset of decrease in ICP within 15\u2009min by 50% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0018) and lasted up to 12\u2009h. The periorbital pain thresholds were higher after 1\u2009h (saline: 224.6\u2009\u00b1\u200915.1 vs caffeine: 289.5\u2009\u00b1\u20098.7\u2009g,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005) and lasted up to 5\u2009h. Caffeine\u2010treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR\n                      <jats:sub>1<\/jats:sub>\n                      was found in the choroid plexus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14634","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T16:07:19Z","timestamp":1696522039000},"page":"1220-1231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of caffeine on intracranial pressure and pain perception in freely moving rats"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-0592","authenticated-orcid":false,"given":"Ida Marchen Egerod","family":"Israelsen","sequence":"first","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Glostrup Research Institute, Rigshospitalet\u2010Glostrup University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5066-8306","authenticated-orcid":false,"given":"Connar Stanley James","family":"Westgate","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Glostrup Research Institute, Rigshospitalet\u2010Glostrup University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-2211","authenticated-orcid":false,"given":"Christina","family":"Kamp\u2010Jensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Glostrup Research Institute, Rigshospitalet\u2010Glostrup University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-5887","authenticated-orcid":false,"given":"Rigmor 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