{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:18:12Z","timestamp":1788157092685,"version":"build-2803163510"},"reference-count":9,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medyceles Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Pain is a major contributor to disability in cervical dystonia (CD) and may persist despite improvement in abnormal head posture after botulinum toxin treatment. Whether increasing the dose of Neubotulinum toxin type A (Neu-BoNT-A) provides additional analgesic benefit without compromising safety remains uncertain. In this prospective, multicenter, randomized, double-blind, two-period crossover trial, 50 adults with CD were randomized 1:1 to Neu-BoNT-A 100 U followed by 50 U or 50 U followed by 100 U, with each treatment period lasting 12 weeks. The principal between-dose TWSTRS analysis used a crossover mixed-effects model including treatment, period, and randomized sequence, with participant as a random effect. TWSTRS total, severity, and disability did not differ significantly between regimens. Neu-BoNT-A 100 U produced greater improvement in TWSTRS pain (adjusted 100 U minus 50 U difference, \u22121.83 points; 95% CI, \u22122.93 to \u22120.73; p = 0.0011). The pain finding remained significant in a robust GEE sensitivity analysis (difference, \u22121.83 points; 95% CI, \u22123.04 to \u22120.62; p = 0.003). CDIP-58 psychosocial functioning also improved more with 100 U (nominal p = 0.001). In a Holm sensitivity analysis across all 24 efficacy comparisons, TWSTRS pain and CDIP-58 psychosocial functioning remained significant (adjusted p \u2248 0.025 and 0.024, respectively); no other comparison remained significant. No serious adverse events occurred. Neu-BoNT-A 100 U did not improve overall CD severity compared with 50 U but was associated with greater pain relief and improved psychosocial functioning without compromising tolerability. These secondary findings remained significant after multiplicity adjustment but should be interpreted in the context of the nonsignificant overall TWSTRS result and require confirmation.<\/jats:p>","DOI":"10.3390\/toxins18090370","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:55:56Z","timestamp":1788155756000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pain-Specific Benefits of Higher-Dose Neubotulinum Toxin Type A in Cervical Dystonia: A Multicenter Randomized Double-Blind Crossover Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Arkhom","family":"Arayawichanont","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani 34000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-1730","authenticated-orcid":false,"given":"Subsai","family":"Kongsaengdao","sequence":"additional","affiliation":[{"name":"Office of Senior Advisor, Department of Medical Services, Ministry of Public Health, Nonthaburi 11000, Thailand"},{"name":"Division of Neurology, Rajavithi Hospital, Department of Medical Services, Ministry of Public Health, Bangkok 10400, Thailand"},{"name":"Division of Neurology, Department of Medicine, College of Medicine, Rangsit University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1080\/14737175.2024.2368638","article-title":"Current use of neurotoxins for alleviating symptoms of cervical dystonia","volume":"24","author":"Aradi","year":"2024","journal-title":"Expert Rev. Neurother."},{"key":"ref_2","first-page":"CD003633","article-title":"Botulinum toxin type A therapy for cervical dystonia","volume":"11","author":"Rodrigues","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s00415-014-7343-6","article-title":"Cervical dystonia and pain: Characteristics and treatment patterns from CD PROBE","volume":"261","author":"Charles","year":"2014","journal-title":"J. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10072-025-08636-3","article-title":"Optimizing treatment for cervical dystonia: Botulinum toxin alone or combined with physical therapy?","volume":"47","author":"Verriello","year":"2026","journal-title":"Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kongsaengdao, S., Arayawithchanont, A., Samintharapanya, K., Rojanapitayakorn, P., Maneeton, B., and Maneeton, N. (2021). Low-dose Neubotulinum toxin A versus low-dose abobotulinum toxin A injection for the treatment of cervical dystonia: A multicenter, 48-week, prospective, double-blinded, randomized crossover design study. Toxins, 13.","DOI":"10.3390\/toxins13100694"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fasano, A., Paramanandam, V., and Jog, M. (2020). Use of abobotulinumtoxinA in adults with cervical dystonia: A systematic literature review. Toxins, 12.","DOI":"10.3390\/toxins12080470"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/ene.13800","article-title":"Quality of life improvements in patients with cervical dystonia following treatment with a liquid formulation of abobotulinumtoxinA (Dysport)","volume":"26","author":"Picaut","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/PRA.0000000000000136","article-title":"Role of botulinum toxin in depression","volume":"22","author":"Parsaik","year":"2016","journal-title":"J. Psychiatr. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s10072-019-3719-9","article-title":"Evaluation of anxiety and depression scales and quality of life in cervical dystonia patients on botulinum toxin therapy and their relatives","volume":"40","author":"Ceylan","year":"2019","journal-title":"Neurol. Sci."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/370\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:07:18Z","timestamp":1788156438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":9,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxins18090370"],"URL":"https:\/\/doi.org\/10.3390\/toxins18090370","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}