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A reported limitation of preclinical models is that they often fail to encapsulate this complexity, and few studies have directly compared behavioral outcomes between male and female mice. The intraplantar Complete Freund's adjuvant (CFA) inflammatory pain model is a widely used preclinical model of persistent mechanical and thermal hypersensitivity, which triggers sex\u2010dependent adaptations in neuronal signaling. However, the literature regarding the duration of pain hypersensitivity and the presence or absence of associated locomotor and anxiety\u2010like changes is inconsistent. Therefore, this study aimed to systematically assess the CFA model's capacity to duplicate pain comorbidities in male and female mice. CFA\u2010injected or saline control male and female mice were assessed over 3\u2009weeks for mechanical and cold nociceptive sensitivity (von Frey and acetone test), locomotion (open field test), and anxiety\u2010like behaviors (light\u2013dark and elevated plus maze tests). CFA\u2010injected mice of both sexes reliably developed mechanical hypersensitivity and cold allodynia. Transient locomotor deficits were observed only in male mice at early timepoints, and no changes in anxiety\u2010like behaviors in either males or females were observed. Hence, the CFA persistent pain model is a practical tool for inducing pronociceptive states in male and female mice but does not reliably produce anxiety\u2010like comorbidities over the tested time periods, suggesting that additional factors may be necessary to elicit these behavioral outcomes.<\/jats:p>","DOI":"10.1002\/jnr.70157","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:29:50Z","timestamp":1789802990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Intraplantar\n                    <scp>CFA<\/scp>\n                    Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes"],"prefix":"10.1002","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1450-8856","authenticated-orcid":false,"given":"Caitlin E.","family":"Fenech","sequence":"first","affiliation":[{"name":"Pain Management Research Laboratories Kolling Institute Royal North Shore Hospital, Northern Sydney Local Health District  St Leonards New South Wales Australia"},{"name":"School of Medical Sciences, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Sydney Pain Consortium, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-0967","authenticated-orcid":false,"given":"Neda","family":"Assareh","sequence":"additional","affiliation":[{"name":"Sydney Pain Consortium, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Brain and Mind Centre, Faculty of Science University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-4041","authenticated-orcid":false,"given":"Karin R.","family":"Aubrey","sequence":"additional","affiliation":[{"name":"Pain Management Research Laboratories Kolling Institute Royal North Shore Hospital, Northern Sydney Local Health District  St Leonards New South Wales Australia"},{"name":"Sydney Pain Consortium, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.0268"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.12.018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpain.2025.1648374"},{"key":"e_1_2_11_5_1","volume-title":"Methods of Behavior Analysis in Neuroscience","author":"Bailey K. 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