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In fact, previous studies applied isolated techniques, which were not representative of common clinical practice. A multimodal approach for migraine may benefit these patients more than isolated approaches. This randomized clinical trial aims to determine the effectiveness of a multimodal protocol combining manual therapy, exercise, and therapeutic pain neuroscience education versus the application of manual therapy or pain neuroscience education alone in patients with migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This clinical trial will include 75 individuals of both sexes, aged between 18 and 55\u00a0years, with migraine. Participants will be randomized into three groups: the therapeutic pain neuroscience education (TPNE;<jats:italic>n<\/jats:italic>\u2009=\u200925) group, the manual therapy (MT;<jats:italic>n<\/jats:italic>\u2009=\u200925) group, and the multimodal (MM;<jats:italic>n<\/jats:italic>\u2009=\u200925) group. The TPNE group will receive one orientation session on migraine and pain self-management, and recommendations for daily active stretching and walking, with subsequent therapist monitoring. The MT group will receive manual therapies targeting musculoskeletal disorders of the cervical spine. The MM group will receive manual therapies targeting musculoskeletal disorders of the cervical spine, active neck exercises, and therapeutic pain neuroscience education. The treatment period will last 12\u00a0weeks. The primary outcome will be the headache impact, measured using the Headache Impact Test (HIT-6). Secondary outcomes will include migraine frequency and intensity, cervical mobility and strength parameters, neck pain-related disability, kinesiophobia, cutaneous allodynia, pain-related catastrophizing, quality of life, and self-perception of change. All outcomes will be evaluated at the fourth, eighth, and twelfth weeks of the treatment period. Primary and secondary clinical outcomes, such as headache impact, frequency, and intensity, will also be evaluated at the 1-, 2-, and 4-month follow-ups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results of this randomized clinical trial may provide high-quality clinical evidence of the effects of non-pharmacological treatment options for the management of migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>This study was registered under the access code<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ensaiosclinicos.gov.br\/trial\/10191\">RBR-7s22c75<\/jats:ext-link>in the<jats:italic>Registro Brasileiro de Ensaios Cl\u00ednicos<\/jats:italic>(ReBEC) in December 2020.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12883-021-02290-w","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T04:02:40Z","timestamp":1624939360000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of combining manual therapy, neck muscle exercises, and therapeutic pain neuroscience education in patients with migraine: a study protocol for a randomized clinical trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Gabriella","family":"de Almeida Tolentino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidiane","family":"Lima Florencio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Ferreira Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edola","family":"Dach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Bevilaqua-Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"2290_CR1","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.ncl.2019.06.001","volume":"37","author":"RC Burch","year":"2019","unstructured":"Burch RC, Buse DC, Lipton RB. 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Any potential change needed in the current protocol should be informed to the Ethics Committee for their approval, and then, it should be communicated to the trial registration. All participants will receive and sign an informed consent form before entering the trial. Personal information privacy will be guaranteed through number codification and date access restricted to the research group.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"249"}}