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Given growing evidence linking endoplasmic reticulum (ER) stress to inflammation and pain sensitization, we examined circulating ER stress-associated heat shock proteins (HSPs) GRP78 and gp96 in individuals with dysmenorrhea (n\u2009=\u200982), a dysmenorrhea subtype with bladder pain sensitivity (DYSB, n\u2009=\u200926) previously shown to increase risk for chronic pain, and controls (n\u2009=\u200919). After correcting for Menstrual phase, naproxen exposure, and oral contraceptive use, GRP78 was higher in DYSB than in DYS (ratio 1.33;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.028), while gp96 was lower in both DYS (ratio 0.62;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.019) and DYSB (ratio 0.59;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.031) compared to controls. gp96 was also lower during the menstrual phase with naproxen compared to the non-menstrual phase (ratio 0.73;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.014), whereas GRP78 was not significantly affected by menstrual phase, naproxen, or oral contraceptive use, and neither protein was associated with anxiety, depression, or sleep disturbance scores. These cross-sectional findings suggest that dysmenorrhea, particularly the bladder-sensitive subtype (DYSB), is associated with divergent circulating levels of two ER stress-related proteins. The inverse pattern of higher GRP78 and lower gp96 levels points to selective, rather than global, ER chaperone dysregulation as a candidate mechanism. However, future mechanistic and longitudinal investigations will be required to establish whether GRP78 and gp96 carry predictive or pathophysiological relevance.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-58824-0","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:34:47Z","timestamp":1782786887000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of circulating GRP78 and gp96, endoplasmic reticulum stress-related proteins, in menstrual and bladder pain sensitivity"],"prefix":"10.1038","volume":"16","author":[{"given":"Chandrashekara N.","family":"Kyathanahalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Darnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank F.","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Hellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"58824_CR1","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/humupd\/dmv039","volume":"21","author":"S Iacovides","year":"2015","unstructured":"Iacovides, S., Avidon, I. & Baker, F. 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