{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:59:03Z","timestamp":1789595943442,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Chronic pain syndromes present a subversion of both functional and structural nociceptive networks. We used transcranial magnetic stimulation (TMS) to evaluate changes in cortical excitability and plasticity in patients with chronic migraine (CM) treated with botulinum neurotoxin type A (BoNT\/A). We enrolled 11 patients with episodic migraine (EM) and 11 affected by CM. Baseline characteristics for both groups were recorded using single- and paired-pulse TMS protocols. The same TMS protocol was repeated in CM patients after four cycles of BoNT\/A completed in one year. At baseline, compared with EM patients, patients with CM had a lower threshold in both hemispheres (right hemisphere: 46% \u00b1 7.8 vs. 52% \u00b1 4.28, p = 0.03; left hemisphere: 52% \u00b1 4.28 vs. 53.54% \u00b1 6.58, p = 0.02). In EM, paired-pulse stimulation elicited a physiologically shaped response, whereas in CM, physiological intracortical inhibition (ICI) between 1 and 3 ms intervals was absent at baseline. On the contrary, increasing intracortical facilitation (ICF) was observed for all interstimulus intervals (ISIs). In CM, cortical excitability was partially reduced after BoNT\/A treatment, along with a significant decrease observed in MIDAS score (from 20.7 to 9.8; p = 0.008). The lower motor threshold in CM reflects a higher cortical hyperexcitability. The lack of physiological ICI in CM could indicate sensitisation of the trigeminovascular system. Although reduced, this type of response is still observable after treatment, despite a marked clinical improvement. Our study suggests a long-term alteration of cortical plasticity due to chronic pain.<\/jats:p>","DOI":"10.3390\/toxins13060392","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T03:45:29Z","timestamp":1622432729000},"page":"392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical and Neurophysiological Effects of Botulinum Neurotoxin Type A in Chronic Migraine"],"prefix":"10.3390","volume":"13","author":[{"given":"Mariarosaria","family":"Valente","sequence":"first","affiliation":[{"name":"Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"},{"name":"Department of Medicine, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-6277","authenticated-orcid":false,"given":"Christian","family":"Lettieri","sequence":"additional","affiliation":[{"name":"Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Russo","sequence":"additional","affiliation":[{"name":"Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"},{"name":"Intensive Rehabilitation Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1534-1409","authenticated-orcid":false,"given":"Francesco","family":"Janes","sequence":"additional","affiliation":[{"name":"Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luigi","family":"Gigli","sequence":"additional","affiliation":[{"name":"Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, 33100 Udine, Italy"},{"name":"Department of Medicine, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neuron.2015.11.027","article-title":"Common Brain Mechanisms of Chronic Pain and Addiction","volume":"89","author":"Elman","year":"2016","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Green, M.W., Cowan, R., and Freitag, F. 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