{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:30:17Z","timestamp":1785933017250,"version":"3.56.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 114\u20102320\u2010B\u2010038\u2010056"],"award-info":[{"award-number":["NSTC 114\u20102320\u2010B\u2010038\u2010056"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["TMU 112\u20105431\u2010002\u2010400"],"award-info":[{"award-number":["TMU 112\u20105431\u2010002\u2010400"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sumatriptan, an antimigraine drug, is known to cause adverse chest symptoms such as dyspnea and chest tightness. We previously showed that sumatriptan sensitized capsaicin\u2010sensitive lung vagal (CSLV) afferents in rats, a mechanism potentially underlying these symptoms. This sensitizing effect was abolished by intravenous GR127935, a 5\u2010HT\n                      <jats:sub>1B\/1D<\/jats:sub>\n                      receptor antagonist. Therefore, to develop a potential therapeutic strategy, we hypothesized that targeting GR127935 to the lungs, rather than delivering it systemically, could prevent sumatriptan\u2010induced chest discomfort by reducing CSLV\u2010afferent sensitization without compromising sumatriptan's antimigraine efficacy within the trigeminovascular system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Experiments were performed in anesthetized male Brown\u2010Norway rats. CSLV\u2010afferent excitability and afferent\u2010mediated airway reflexes were assessed using single\u2010fiber recordings and respiratory pattern monitoring. The antimigraine efficacy of sumatriptan was evaluated based on its inhibitory effect on dural plasma protein extravasation evoked by unilateral electrical stimulation of the trigeminal ganglion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Intravenous sumatriptan potentiated capsaicin\u2010evoked CSLV\u2010afferent discharges and afferent\u2010mediated airway responses. However, pretreatment with inhaled GR127935 significantly blocked this potentiating effect. The sumatriptan's antimigraine efficacy was not affected by inhaled GR127935, but was reduced by intravenous GR127935. Consistently, intravenous, but not inhaled GR127935, altered sumatriptan\u2010induced hypotension, indicating that pulmonary delivery minimized systemic effects. Moreover, inhaled GR127935 did not change baseline cardiorespiratory parameters or fiber activity, suggesting it is unlikely to cause adverse cardiorespiratory effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Inhalation of a 5\u2010HT\n                      <jats:sub>1B\/1D<\/jats:sub>\n                      receptor antagonist effectively prevented sumatriptan\u2010induced sensitization of CSLV afferents without diminishing sumatriptan's antimigraine efficacy. Our findings suggest that inhaled 5\u2010HT\n                      <jats:sub>1B\/1D<\/jats:sub>\n                      antagonists may offer a promising strategy to prevent or treat sumatriptan\u2010induced adverse chest symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70121","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:47:04Z","timestamp":1773298024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhaled 5\u2010\n                    <scp>\n                      HT\n                      <sub>1B<\/sub>\n                    <\/scp>\n                    <sub>\n                      \/\n                      <scp>1D<\/scp>\n                    <\/sub>\n                    Receptor Antagonist Attenuates Sumatriptan\u2010Induced Sensitization of Capsaicin\u2010Sensitive Lung Vagal Afferents: Implications for Preventing Sumatriptan\u2010Associated Adverse Chest Symptoms"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-9761","authenticated-orcid":false,"given":"Nai\u2010Ju","family":"Chan","sequence":"first","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Department of Physiology School of Medicine, College of Medicine, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zung Fan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Master Program in Biomedical Sciences School of Medicine, Tzu Chi University  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Chih","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Master Program in Biomedical Sciences School of Medicine, Tzu Chi University  Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2319-2151","authenticated-orcid":false,"given":"Chun\u2010Chun","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University  Taipei Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine Taipei Medical University Hospital, Taipei Medical University  Taipei 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