{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:06:18Z","timestamp":1775117178176,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives\/Background<\/jats:title>\n                    <jats:p>Chronic migraine is a debilitating neurological disorder characterized by central sensitization and impaired brainstem habituation. OnabotulinumtoxinA is an established prophylactic treatment for chronic migraine, yet its effects on central trigeminal sensory processing remain incompletely understood. The nociceptive blink reflex (nBR) is a well\u2010established neurophysiological tool for assessing brainstem excitability and central sensory processing within the trigeminal system. This prospective case\u2013control study investigated longitudinal changes in brainstem neurophysiology following onabotulinumtoxinA treatment using the nBR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between November 2022 and April 2024, we assessed nBR habituation in 27 patients with chronic migraine and compared them with 27 age\u2010 and sex\u2010matched healthy controls. Measurements were performed at peak efficacy (1 month postinjection, Month 1+) and prior to reinjection (3 months postinjection, Month 3+). Habituation of the polysynaptic R2 response was analyzed as the primary outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At Month 1+, R2 nBR habituation in patients was similar to that observed in healthy controls (4\u2010s interstimulus interval, ipsilateral:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.10, 95% confidence interval [CI] = \u22120.16 to 0.36,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.457); however, by Month 3+, patients showed a significant impairment in R2 habituation compared to healthy controls (4\u2010s interstimulus interval, ipsilateral:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.29, 95% CI = \u22120.55 to \u22120.03,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029). Correlation analyses revealed that reduced habituation was associated with increased monthly migraine days (4\u2010s interstimulus interval, contralateral:\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.41, 95% CI\u2009=\u20090.02 to 0.69,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.039) and prolonged intervals since the last onabotulinumtoxinA treatment (4\u2010s interstimulus interval, Month 3+, ipsilateral:\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.33, 95% CI\u2009=\u20090.06 to 0.55,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018), which aligns with the clinical observation of wearing off. Supporting this notion, patients with more prior treatment cycles exhibited sustained improvement in habituation deficits (4\u2010s interstimulus interval, Month 3+, ipsilateral:\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.46, 95% CI = \u22120.71 to \u22120.09,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017). The monosynaptic R1 component remained unchanged between Month 1+ and 3+ (4\u2010s interstimulus interval, ipsilateral:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.028, 95% CI = \u22120.067 to 0.011,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.164), emphasizing a specific treatment effect of trigeminal system\u2010mediated pain processing at the brainstem level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that onabotulinumtoxinA exerts a neuromodulatory effect on brainstem neurophysiology, with R2 habituation improving during peak treatment efficacy and declining as the effect wears off. The results underscore the time\u2010dependent central effects of onabotulinumtoxinA on nociceptive processing within the trigeminal system. Future research should investigate the nBR as a potential biomarker for optimizing onabotulinumtoxinA treatment strategies in chronic migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.15021","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T17:18:26Z","timestamp":1752599906000},"page":"950-962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in brainstem habituation during\n                    <scp>onabotulinumtoxinA<\/scp>\n                    treatment in chronic migraine: A prospective case\u2013control study"],"prefix":"10.1111","volume":"66","author":[{"given":"Gerlinde","family":"Freimark","sequence":"first","affiliation":[{"name":"Department of Neurology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin 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