{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:50:15Z","timestamp":1781941815991,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"publisher","award":["3527"],"award-info":[{"award-number":["3527"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303816\/2023\u20106"],"award-info":[{"award-number":["303816\/2023\u20106"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["code 001"],"award-info":[{"award-number":["code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study explores whether sleep restriction (SR) and caffeine intake affect migraine susceptibility by testing if each condition, alone or in combination, precipitates migraine\u2010like responses to subthreshold doses of calcitonin gene\u2010related peptide (CGRP) or pituitary adenylate cyclase\u2010activating polypeptide (PACAP) in male and female rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a debilitating neurological syndrome that affects approximately 15% of the global population, with a three\u2010fold higher prevalence in females compared to males. Among the peripheral mechanisms underlying migraine, the release of vasoactive peptides by trigeminal ganglion (TG) neurons, such as CGRP and PACAP, plays a crucial role. Various environmental triggers\u2014including sleep or food deprivation, caffeine intake or withdrawal, stress, and light exposure\u2014have been associated with the onset of migraine attacks; however, the mechanisms by which these factors modulate nociceptive sensitization remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female Wistar rats were subjected to SR for 6\u2009h daily over 3 consecutive days using the gentle handling method, and the periorbital mechanical allodynia was assessed using von Frey filaments before and after each day of SR. Next, a subthreshold dose of CGRP (38\u2009ng\/10\u2009\u03bcL) or PACAP (0.1\u2009ng\/10\u2009\u03bcL) was administered into the TG on the third day of SR to evaluate whether sleep loss enhances susceptibility to migraine\u2010like responses. Finally, two additional experiments were conducted to investigate the influence of caffeine (50\u2009mg\/kg, orally) exposure in combination of SR in CGRP and PACAP effects. In all experiments, on day 4 (i.e., 24\u2009h after the last SR), the animals were exposed for 1\u2009h to an aversive light for verification of latent sensitization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results demonstrated that SR alone did not alter the periorbital mechanical threshold in either male or female rats. However, when SR was combined with the administration of CGRP or PACAP at subthreshold doses, a significant periorbital mechanical allodynia developed in female, but not in male rats. The exposure to light in the subsequent day caused a transitory reactivation of mechanical allodynia only in females. In well\u2010rested animals, a 3\u2010day caffeine regimen enabled behaviorally subthreshold doses of CGRP or PACAP to elicit migraine\u2010like responses in females, but not in males. In sleep\u2010restricted animals, combining caffeine with subthreshold doses of CGRP or PACAP rendered males susceptible to migraine\u2010like responses and markedly exacerbated these responses in females, including 1 day later, after light exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest that SR facilitates trigeminovascular sensitization, promoting migraine\u2010like responses in a sex\u2010specific manner and highlighting caffeine as an enhancer of this interaction. Beyond reinforcing the association between poor sleep and migraine, the data offer new insights into the involvement of the purinergic system and sex differences in migraine pathophysiology.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/head70099-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70099","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:35:36Z","timestamp":1775799336000},"page":"1363-1375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lifestyle triggers of migraine: Sleep restriction and caffeine lower the threshold for migraine\u2010like responses in rats in a sex\u2010specific manner"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8720-393X","authenticated-orcid":false,"given":"Gabriel Camargo","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darciane Favero","family":"Baggio","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Bordenowsky Pereira","family":"Lejeune","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Storithont","family":"Quinelato","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Mariano Ribeiro","family":"da Luz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander Roberto","family":"Zampronio","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Physiology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-141X","authenticated-orcid":false,"given":"Juliana Geremias","family":"Chichorro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00763-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241511993"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-01011-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14595"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419896539"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024251386794"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-024-01290-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsmc.2022.03.003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01192-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae051"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2016.01.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.01002"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-017-0806-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-018-0867-x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-3057(97)00595-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702202"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4329"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.06.022"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110055"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01921-0"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0364-19.2019"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1603758"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01771-w"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419865252"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413515344"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2334\/josnusd.18-0031"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024211014633"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2200-20.2021"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01569-2"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01155-w"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2022.04.004"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221148391"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2025.100727"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024241281493"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020344"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2016.04.005"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12082259"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2962"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61421-8"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2016.591"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1986.tb16267.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.6.1533"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf141"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.70099","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/head.70099","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.70099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:02:19Z","timestamp":1781938939000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.70099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/head.70099"],"URL":"https:\/\/doi.org\/10.1111\/head.70099","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"assertion":[{"value":"2025-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}