{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:26:32Z","timestamp":1765517192086,"version":"3.48.0"},"reference-count":60,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the widespread use of experimental acute pain models, little exploration has been undertaken on the acute pain proteome in humans. We resolved to explore molecular alterations evoked by hypertonic saline (HS)-induced acute muscle pain and to map the spread of mechanical hyperalgesia. This study used a two-cohort design in healthy participants. Cohort one (n = 16) underwent intermittent blood sampling prior to, during, and following intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n = 10) underwent bilateral sensory testing during HS infusion, to map the spread of mechanical hyperalgesia. Molecular analysis in cohort one revealed a broad array of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly, these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Cohort two revealed a significant mechanical hyperalgesia which emerged in a distributed pattern over the ipsilateral limb to HS infusion. However, despite systemic molecular alterations, no such mechanical hyperalgesia was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute HS-induced muscle pain, accompanied by spatially constrained sensory interactions. This dissociation implies that, at least in acute sensitization, widespread molecular changes may not necessarily translate into a correspondingly widespread sensory phenotype.<\/jats:p>","DOI":"10.3390\/ijms262411922","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:32:17Z","timestamp":1765380737000},"page":"11922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Proteome of Acute Muscle Pain: Observations from Acute Hypertonic-Saline-Induced Pain in Humans"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-257X","authenticated-orcid":false,"given":"Pauline","family":"Jubin","sequence":"first","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3626-0273","authenticated-orcid":false,"given":"Marie","family":"Amigo","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-2469","authenticated-orcid":false,"given":"Daniel","family":"Boulton","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-9638","authenticated-orcid":false,"given":"David A.","family":"Mahns","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-8232","authenticated-orcid":false,"given":"Saad S.","family":"Nagi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 582 25 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-2996","authenticated-orcid":false,"given":"James S.","family":"Dunn","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1172\/JCI102815","article-title":"Observations on pain produced by injection of hypertonic saline into muscles and other supportive tissues","volume":"32","author":"Steinbrocker","year":"1953","journal-title":"J. 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