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OnabotulinumtoxinA (onbotA) is used to treat chronic migraine but the mechanism of action is not fully understood. Here we investigate the role of meningeal MPs in a model of migraine activation and evaluate whether onabotA has an effect on their response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We use our previously developed method to determine meningeal MP activation based on shape changes using time-lapse in vivo multiphoton microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that a small subset (\u223c10%) of MPs contracted their processes in response to CSD induction, but only in female mice. A similar subset of MPs contracted with lipopolysaccharide injection, suggesting that this is an M1-like response. Together this may provide insight into the phenotypic differences of migraine across males and females. We also found a small subset of MPs (\u223c10%) that expanded their processes in response to IL-10 (presumably an M2-like response), but were not affected by CSD. In female mice, pre-treatment with onabotA (i) reduces overall MP number in the dura, (ii) reduces pro-inflammatory M1 MP response and (iii) increases anti-inflammatory M2 response post-CSD compared to pretreatment with saline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This suggests that the mechanism of action of onabotA may not be simply due to its effects on nociceptors, but also due to an additional anti-inflammatory effect on the environment of the dura.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024251378730","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T18:43:33Z","timestamp":1758912213000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["OnabotulinumtoxinA alters pro- and anti-inflammatory dural macrophage response to CSD in female mice"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7707-3556","authenticated-orcid":false,"given":"Aaron J.","family":"Schain","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4296-0734","authenticated-orcid":false,"given":"Diego","family":"Delgado Fajardo","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Strassman","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1747-0116","authenticated-orcid":false,"given":"Ron S.","family":"Broide","sequence":"additional","affiliation":[{"name":"Allergan\/AbbVie, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Brideau-Andersen","sequence":"additional","affiliation":[{"name":"Allergan\/AbbVie, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey Manack","family":"Adams","sequence":"additional","affiliation":[{"name":"Allergan\/AbbVie, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-6076","authenticated-orcid":false,"given":"Mitchell F.","family":"Brin","sequence":"additional","affiliation":[{"name":"Allergan\/AbbVie, Irvine, CA, USA"},{"name":"Department of Neurology, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-8916","authenticated-orcid":false,"given":"Rami","family":"Burstein","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_3_2_2_2","volume-title":"The Headaches","author":"Olesen J","year":"2006","unstructured":"Olesen J (ed). 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