{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:02Z","timestamp":1760059022846,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background\/Objectives: Studying the second exteroceptive suppression period (ES2) of the temporalis muscle may well shed some light on the brainstem neural circuits involved in migraine pathophysiology. It is known that allodynia is related to an increased sensitization of second-\/third-order neurons both in the trigeminal nucleus caudalis and sensory thalamus. This pilot, observational study was carried out in the interictal period on female migraineurs with\/without allodynia to assess the ES2 of the temporalis muscle compared to controls. Methods: Forty-nine non-consecutive female patients were enrolled, as they met the diagnostic criteria for migraine (26 episodic and 23 chronic), alongside 23 healthy controls. The inclusion criteria encompassed no ongoing pharmacological prophylactic treatment, and the exclusion criteria included any relevant comorbidities. In line with international standards, the exteroceptive suppression of the temporalis muscle activity was registered on the left side, assessing ES2 latency and duration in the interictal period. Results: Allodynia was observed in 24 patients (50%), and 16\/24 (67%) were chronic migraineurs. No statistically significant differences in ES2 latency or its duration between the migraine patients and controls were detected. However, there was a significantly longer ES2 duration in allodynic migraineurs than in the controls (p = 0.04; effect size: 0.71) and in allodynic compared to non-allodynic migraineurs (p = 0.04; effect size: 0.63). Conclusions: The increased duration of ES2 observed in allodynic migraineurs might be related to the impaired activity of brainstem circuits and, in our opinion, it seems reasonable to hypothesize that this change may be a neurophysiological correlate of central sensitization in migraine allodynic patients.<\/jats:p>","DOI":"10.3390\/neurolint17050076","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"76","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Second Exteroceptive Suppression Period of the Temporalis Muscle Is Altered in Migraine Patients with Allodynia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-7634","authenticated-orcid":false,"given":"Eugenia","family":"Rota","sequence":"first","affiliation":[{"name":"Neurology Unit, San Giacomo Hospital, 15067 Novi Ligure, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-3903","authenticated-orcid":false,"given":"Paolo","family":"Immovilli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Aguggia","sequence":"additional","affiliation":[{"name":"Neurology Unit, Cardinal Massaia Hospital, 14100 Asti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Gabriella","family":"Saracco","sequence":"additional","affiliation":[{"name":"Neurology Unit, San Giacomo Hospital, 15067 Novi Ligure, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Ghiglione","sequence":"additional","affiliation":[{"name":"Neurology Unit, San Giacomo Hospital, 15067 Novi Ligure, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Melotti","sequence":"additional","affiliation":[{"name":"Neurology Unit, San Giacomo Hospital, 15067 Novi Ligure, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3787-2243","authenticated-orcid":false,"given":"Nicola","family":"Morelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3331024241267309","DOI":"10.1177\/03331024241267309","article-title":"Migraine is the most disabling neurological disease among children and adolescents, and second after stroke among adults: A call to action","volume":"44","author":"Peres","year":"2024","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1129-2377-14-65","article-title":"Habituation and sensitization in primary headaches","volume":"14","author":"Coppola","year":"2013","journal-title":"J. Headache Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1016\/j.pain.2013.07.021","article-title":"Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain","volume":"154","author":"Noseda","year":"2013","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1526-4610.2007.00969.x","article-title":"Concepts and mechanisms of migraine chronification","volume":"48","author":"Bigal","year":"2008","journal-title":"Headache"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0140-6736(18)30478-1","article-title":"Migraine","volume":"391","author":"Dodick","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1152\/jn.1998.79.2.964","article-title":"Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons","volume":"9","author":"Burstein","year":"1998","journal-title":"J. Neurophysiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/1531-8249(200005)47:5<614::AID-ANA9>3.0.CO;2-N","article-title":"An association between migraine and cutaneous allodynia","volume":"47","author":"Burstein","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0006-8993(91)90886-Z","article-title":"Periaqueductal gray matter and nucleus raphe magnus involvement in anterior pretectal nucleus-induced inhibition of jaw-opening reflex in rats","volume":"544","author":"Chiang","year":"1991","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1468-2982.1993.1301003.x","article-title":"Exteroceptive suppression of temporalis muscle activity: Methodological and physiological aspects","volume":"13","author":"Schoenen","year":"1993","journal-title":"Cephalalgia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0079-6123(08)62143-3","article-title":"Pain modulation: Expectation, opioid analgesia and virtual pain","volume":"122","author":"Fields","year":"2000","journal-title":"Prog. Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0306-4522(01)00303-7","article-title":"The periaqueductal grey matter modulates trigeminovascular input: A role in migraine?","volume":"106","author":"Knight","year":"2001","journal-title":"Neuroscience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0959-4388(02)00313-6","article-title":"Brain mechanisms of pain affect and pain modulation","volume":"12","author":"Rainville","year":"2002","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1111\/j.1526-4610.2005.00244.x","article-title":"Changes in cortical processing of pain in chronic migraine","volume":"45","author":"Losito","year":"2005","journal-title":"Headache"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1212\/WNL.61.8_suppl_4.S2","article-title":"Contemporary concepts of migraine pathogenesis","volume":"61","author":"Welch","year":"2003","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1388-2457(99)00291-6","article-title":"The clinical use of brainstem reflex and hand-muscle reflexes","volume":"111","author":"Cruccu","year":"2000","journal-title":"Clin. Neurophysiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/brain\/awh366","article-title":"Brainstem reflex circuits revisited","volume":"128","author":"Cruccu","year":"2005","journal-title":"Brain"},{"doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia, 38, 1\u2013211.","key":"ref_17","DOI":"10.1177\/0333102417738202"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1046\/j.1468-2982.1993.1301020.x","article-title":"Exteroceptive suppression in headache research. Discussion summary","volume":"13","author":"Schoenen","year":"1993","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1526-4610.1995.hed3506338.x","article-title":"Exteroceptive suppression of temporalis muscle activity: A blind study of tension-type headache, migraine, and cervicogenic headache","volume":"35","author":"Zwart","year":"1995","journal-title":"Headache"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/head.13677","article-title":"Allodynia in menstrually related migraine: Score assessment by Allodynia symptom checklist (ASC-12)","volume":"60","author":"Melhado","year":"2020","journal-title":"Headache"},{"doi-asserted-by":"crossref","unstructured":"M\u00ednguez-Olaondo, A., Quintas, S., Moroll\u00f3n S\u00e1nchez-Mateos, N., L\u00f3pez-Bravo, A., Vila-Pueyo, M., Grozeva, V., Belv\u00eds, R., Santos-Lasaosa, S., and Irimia, P. (2022). Cutaneous Allodynia in Migraine: A Narrative Review. Front. Neurol., 12.","key":"ref_21","DOI":"10.3389\/fneur.2021.831035"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1212\/WNL.37.12.1834","article-title":"Exteroceptive suppression of temporalis muscle activity in chronic headache","volume":"37","author":"Schoenen","year":"1987","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1046\/j.1526-4610.2001.111006142.x","article-title":"Recovery cycle of the blink reflex and exteroceptive suppression of temporalis muscle activity in migraine and tension-type headache","volume":"41","author":"Aktekin","year":"2001","journal-title":"Headache"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/j.1468-2982.2006.01099.x","article-title":"Exteroceptive suppression of masseter muscle activity in juvenile migraineurs","volume":"26","author":"Ebinger","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1046\/j.1468-2982.2002.00389.x","article-title":"Exteroceptive suppression patterns of masseter and temporalis muscles in central and peripheral headache disorders","volume":"22","author":"Tataroglu","year":"2002","journal-title":"Cephalalgia"},{"key":"ref_26","first-page":"146","article-title":"Blink Reflex in Episodic and Chronic Migraine","volume":"55","author":"Polat","year":"2018","journal-title":"Noro Psikiyatr. Ars."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neucli.2016.09.002","article-title":"Deficient prepulse inhibition of blink reflex in migraine and its relation to allodynia","volume":"47","author":"Uygunoglu","year":"2017","journal-title":"Neurophysiol. Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11642","DOI":"10.1523\/JNEUROSCI.2638-08.2008","article-title":"Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans","volume":"28","author":"Lee","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.clinph.2024.02.006","article-title":"The blink reflex and its modulation\u2014Part 2: Pathophysiology and clinical utility","volume":"160","author":"Gunduz","year":"2024","journal-title":"Clin. Neurophysiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1177\/0333102491011S1109","article-title":"Pharmacologic modulation of temporalis exteroceptive silent periods in healthy volunteers","volume":"11","author":"Schoenen","year":"1991","journal-title":"Cephalalgia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1046\/j.1468-2982.1993.1303151.x","article-title":"On serotonin and migraine: A clinical and pharmacological review","volume":"13","author":"Ferrari","year":"1993","journal-title":"Cephalalgia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00210-022-02216-4","article-title":"Change in the second exteroceptive suppression period of the temporalis muscle during erenumab treatment","volume":"395","author":"Rota","year":"2022","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1177\/03331024221103811","article-title":"The monoclonal CGRP-receptor blocking antibody erenumab has different effects on brainstem and cortical sensory-evoked responses","volume":"42","author":"Casillo","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s10194-021-01364-x","article-title":"Preventive treatment with CGRP monoclonal antibodies restores brain stem habituation deficits and excitability to painful stimuli in migraine: Results from a prospective case-control study","volume":"22","author":"Thiele","year":"2021","journal-title":"J. Headache Pain"},{"doi-asserted-by":"crossref","unstructured":"Danno, D., Imai, N., Kitamura, S., Ishizaki, K., Kikui, S., and Takeshima, T. (2024). Efficacy of galcanezumab in migraine central sensitization. Sci. Rep., 14.","key":"ref_35","DOI":"10.1038\/s41598-024-72282-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1212\/WNL.58.8.1234","article-title":"Acute migraine headache: Possible sensitization of neurons in the spinal trigeminal nucleus?","volume":"58","author":"Kaube","year":"2002","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6222","DOI":"10.2174\/0929867325666180627130811","article-title":"Electrophysiological Characteristics of the Migraine Brain: Current Knowledge and Perspectives","volume":"26","author":"Marucco","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s10194-019-0997-9","article-title":"Clinical neurophysiology of migraine with aura","volume":"20","author":"Coppola","year":"2019","journal-title":"J. Headache Pain"}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/5\/76\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:34:17Z","timestamp":1760031257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/5\/76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["neurolint17050076"],"URL":"https:\/\/doi.org\/10.3390\/neurolint17050076","relation":{},"ISSN":["2035-8377"],"issn-type":[{"type":"electronic","value":"2035-8377"}],"subject":[],"published":{"date-parts":[[2025,5,16]]}}}