{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:36:41Z","timestamp":1792805801485,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Poor sleep and pain perpetuate each other through a feed\u2010forward cycle. While mechanisms driving this cycle remain poorly understood, they appear to involve inflammatory pathways. We investigated whether pre\u2010emptive administration of low\u2010dose acetylsalicylic acid (ASA, aspirin), which targets multiple inflammatory pathways, attenuates the pain response to a sleep restriction challenge in healthy adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty\u2010six participants completed a randomized, double\u2010blind crossover protocol consisting of three conditions: sleep restriction\/ASA, sleep restriction\/placebo, and control sleep\/placebo. Each participant completed all three conditions in randomized order. Study medication was administered throughout both the 14\u2010day at\u2010home phase and the subsequent 11\u2010day laboratory stay. Sleep restriction consisted of five consecutive nights of 4\u2010h sleep opportunity. Pain measures included spontaneous daily pain ratings and quantitative sensory testing assessing pain thresholds, pain tolerance, and central pain modulation (inhibition and facilitation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Low\u2010dose ASA intake for 14\u2009days did not affect baseline assessments of spontaneous pain, pain sensitivity, or modulation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). However, ASA attenuated the pain response to sleep restriction, as evidenced by lower widespread and muscle pain ratings (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009 for condition effect) and less impaired central pain inhibition (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020 for condition \u00d7 day effect) compared to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pre\u2010emptive low\u2010dose ASA attenuated pain responses to sleep restriction, particularly widespread pain and impaired central pain inhibition, consistent with modulation of nociplastic\u2010like pain mechanisms. Elucidating the mechanisms underlying this effect of ASA could help inform the development of targeted strategies for individuals who experience recurrent short or disrupted sleep and may be at increased risk for chronic pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Pre\u2010emptive low\u2010dose acetylsalicylic acid attenuated increases in spontaneous pain, heat pain sensitivity, and impaired central pain inhibition induced by experimental sleep restriction in healthy individuals. These findings suggest that inflammatory modulation may contribute to pain responses following sleep restriction and highlight a potential pathway for mitigating the sleep\u2010related pain vulnerability.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (NCT03377543)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70392","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:20:39Z","timestamp":1790245239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Low\u2010Dose Acetylsalicylic Acid on Spontaneous Pain, Pain Sensitivity, and Central Pain Modulation in Response to a Sleep Restriction Challenge in Healthy Individuals"],"prefix":"10.1002","volume":"30","author":[{"given":"Samantha","family":"Nett","sequence":"first","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rammy","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa C.","family":"Engert","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Division of Sleep Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maham","family":"Taj","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navil","family":"Sethna","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital, Department of Anesthesiology Critical Care and Pain Medicine  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-4294","authenticated-orcid":false,"given":"Monika","family":"Haack","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Division of Sleep Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2017.08.001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.34"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1090"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2022.101695"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.4983"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020219"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000910"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000551037"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.07.023"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.06.018"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001664"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2013.08.007"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsad061"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2011.07.007"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0439-z"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.10.023"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002130"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa169"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/clockssleep4040050"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8052854"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002324"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2020.05.030"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnw300"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000314"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.21037\/apm\u201021\u20101648"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2018.05.023"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00009-6"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2018.10.008"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900477"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0000000000000055"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S460566"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.1.180.180"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7215a1"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare12222300"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2023.101835"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003279"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97943"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001053"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12102"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.03.028"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.07.005"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.605"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.70392","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejp.70392","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejp.70392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:23:01Z","timestamp":1792585381000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejp.70392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ejp.70392"],"URL":"https:\/\/doi.org\/10.1002\/ejp.70392","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"assertion":[{"value":"2026-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70392"}}