{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:53:10Z","timestamp":1791003190434,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":238,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Depression and Anxiety"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Substance P (SP) and neurokinin\u20101 receptor (NK\u20101R) as biomarkers of pain and stress<\/jats:title>\n                    <jats:p>SP and NK\u20101R are neuropeptide related biomarkers involved in nociceptive pathways. Dysmenorrhea is frequently associated with psychological distress and biochemical alterations; however, their interrelationship across treatment phases remains insufficiently understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To explore changes in psychological status (depression, anxiety, and stress), nutritional status, and SP\/NK\u20101R\u2010related biomarker levels across NSAID and dexamethasone plus aprepitant combination therapy phases in females with dysmenorrhea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a randomized, sequential, within\u2010subject repeated\u2010measures crossover exploratory controlled trial with a parallel healthy control group. A total of 40 females were enrolled, including 30 with primary dysmenorrhea and 10 healthy controls. Dysmenorrhea participants were assessed over three menstrual cycles across three phases: baseline (no treatment), NSAID phase (ibuprofen 400\u2009mg three times daily for 3 days), and combination therapy phase (dexamethasone plus aprepitant for 2 days). Psychological status was assessed using DASS\u201021, and nutritional status using the mini nutritional assessment (MNA). Serum SP and NK\u20101R levels were measured using ELISA in a subset of participants due to sample limitations. Data were analyzed using IBM SPSS Statistics (version 22), with repeated\u2010measures ANOVA and independent\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009 &lt; 0.05 was considered statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Participants with dysmenorrhea were enrolled and assessed for ELISA based SP levels in blood. SP levels showed significant variation across treatment phases (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.021), with the lowest values observed during the dexamethasone plus aprepitant phase compared to baseline and NSAID phases. NK\u20101R levels did not show significant phase\u2010wise changes. Psychological subgroup analyses indicated greater SP variability in participants with moderate depression, stress, and anxiety, although several subgroups were small. Nutritional status showed partial associations with SP changes, with significant differences in malnourished and normal groups. Overall, biomarker changes were more pronounced than NK\u20101R alterations across phases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates phase\u2010dependent changes in SP levels alongside psychological and nutritional variations in women with dysmenorrhea. However, absence of clinical pain outcomes and small subgroup sizes limit causal interpretation, and findings should be considered preliminary and biomarker\u2010focused.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/da\/9538518","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:09:25Z","timestamp":1787828965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Depression, Nutritional Status, and Substance P\/NK\u20101R Biomarkers in Dysmenorrhea: A Randomized Crossover Trial"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-1587","authenticated-orcid":false,"given":"Riffat","family":"Mehboob","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-3224","authenticated-orcid":false,"given":"Imran","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1900-0559","authenticated-orcid":false,"given":"Akash","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-593X","authenticated-orcid":false,"given":"Shahzad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4139-2880","authenticated-orcid":false,"given":"Zeeshan","family":"Mehboob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3516-3057","authenticated-orcid":false,"given":"Shadi Ahmed","family":"Alahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0111-8655","authenticated-orcid":false,"given":"Hisham","family":"Nasief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6395-5183","authenticated-orcid":false,"given":"Ahmad","family":"Alwazzan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0296-2236","authenticated-orcid":false,"given":"Khalid A.","family":"Khadawardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Almansouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Mogharbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv039"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-021-01532-w"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.16921"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.22074\/ijfs.2022.542056.1216"},{"key":"e_1_2_9_5_2","article-title":"Baseline Characteristics of Menstruation Among Adolescent Girls of Delhi","volume":"18","author":"Gupta U.","year":"2022","journal-title":"Antrocom: 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