{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:21:49Z","timestamp":1777998109485,"version":"3.51.4"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R37 NS079678"],"award-info":[{"award-number":["R37 NS079678"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1 NS094198"],"award-info":[{"award-number":["RO1 NS094198"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1 NS106345"],"award-info":[{"award-number":["RO1 NS106345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Occipital headache, the perception of pain in the back of the head, is commonly described by patients diagnosed with migraine, tension-type headache, and occipital neuralgia. The greater and lesser occipital nerves play central role in the pathophysiology of occipital headache. In the clinical setup, such headaches are often treated with onabotulinumtoxinA, a neurotoxin capable of disrupting ability of nociceptors to get activated and\/or release proinflammatory neuropeptides. Attempting to understand better onabotulinumtoxinA mechanism of action in reducing headache frequency, we sought to determine its effects on expression of inflammatory genes in injected occipital tissues.<\/jats:p>\n               <jats:p>To achieve this goal, we injected 40 units of onabotulinumtoxinA into four muscle groups (occipitalis, splenius capitis, semispinalis capitis, and trapezius muscles\u2014all located on one side of the occiput) of patients with chronic bilateral occipital headache scheduled for occipital nerve decompression surgery 1 month later. At the time of surgery, we collected discarded muscle, fascia and periosteum tissues from respective locations on both sides of the neck and occiput and performed targeted transcriptome analyses to determine expression level of inflammatory genes in onabotulinumtoxinA-injected and onabotulinumA-uninjected tissues.<\/jats:p>\n               <jats:p>We found that (i) onabotulinumtoxinA alters expression of inflammatory genes largely in periosteum, minimally in muscle and not at all in fascia; (ii) expression of inflammatory genes in uninjected periosteum and muscle is significantly higher in historical onabotulinumA responders than historical non-responders; (iii) in historical responders\u2019 periosteum, onabotulinumA decreases expression of nearly all significantly altered genes, gene sets that define well recognized inflammatory pathways (e.g. pathways involved in adaptive\/innate immune response, lymphocyte activation, and cytokine, chemokine, NF-kB, TNF and interferon signalling), and abundance of 12 different immune cell classes (e.g. neutrophils, macrophages, cytotoxic T-, NK-, Th1-, B- and dendritic-cells), whereas in historical non-responders it increases gene expression but to a level that is nearly identical to the level observed in the uninjected periosteum and muscle of historical responders; and surprisingly (iv) that the anti-inflammatory effects of onabotulinumA are far less apparent in muscles and absent in fascia.<\/jats:p>\n               <jats:p>These findings suggest that in historical responders\u2019 periosteum\u2014but not muscle or fascia\u2014inflammation contributes to the pathophysiology of occipital headache, and that further consideration should be given to the possibility that onabotulinumA mechanism of action in migraine prevention could also be achieved through its ability to reduce pre-existing inflammation, likely through localized interaction that lead to reduction in abundance of immune cells in the calvarial periosteum.<\/jats:p>","DOI":"10.1093\/brain\/awab461","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T04:23:49Z","timestamp":1639801429000},"page":"2436-2449","source":"Crossref","is-referenced-by-count":30,"title":["OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients"],"prefix":"10.1093","volume":"145","author":[{"given":"Lisa","family":"Gfrerer","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital , Boston, MA 02114 , USA"},{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanostring Technologies, Inc. , Seattle, WA, 98109 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"William","family":"Austen","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital , Boston, MA 02114 , USA"},{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-6640","authenticated-orcid":false,"given":"Sait","family":"Ashina","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agustin","family":"Melo-Carrillo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Serena","family":"Longhi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aubrey Manack","family":"Adams","sequence":"additional","affiliation":[{"name":"Abbvie , Madison, NJ 07940 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Houle","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical care and Pain Medicine, Massachusetts General Hospital , Boston, MA 02114 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell F","family":"Brin","sequence":"additional","affiliation":[{"name":"Abbvie , Madison, NJ 07940 , USA"},{"name":"Department of Neurology, University of California , Irvine 92697 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-8916","authenticated-orcid":false,"given":"Rami","family":"Burstein","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"issue":"5","key":"2022072919100212100_awab461-B1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1526-4610.1978.hed1805268.x","article-title":"Some clinical features of the acute migraine attack. 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