{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:43:33Z","timestamp":1791474213100,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Growing evidence indicates that the parasympathetic system is implicated in migraine headache. However, the cholinergic mechanisms in the pathophysiology of migraine remain unclear. We investigated the effects and mechanisms of cholinergic modulation and a mast cell stabilizer cromolyn in the nitroglycerin\u2010induced in vivo migraine model and in vitro hemiskull preparations in rats. Effects of cholinergic agents (acetylcholinesterase inhibitor neostigmine, or acetylcholine, and muscarinic antagonist atropine) and mast cell stabilizer cromolyn or their combinations were tested in the in vivo and in vitro experiments. The mechanical hyperalgesia was assessed by von Frey hairs. Calcitonin gene\u2010related peptide (CGRP) and C\u2010fos levels were measured by enzyme\u2010linked immunosorbent assay. Degranulation and count of meningeal mast cells were determined by toluidine\u2010blue staining. Neostigmine augmented the nitroglycerin\u2010induced mechanical hyperalgesia, trigeminal ganglion CGRP levels, brainstem CGRP, and C\u2010fos levels, as well as degranulation of mast cells in vivo. Atropine inhibited neostigmine\u2010induced additional increases in CGRP levels in trigeminal ganglion and brainstem while it failed to do this in the mechanical hyperalgesia, C\u2010fos levels, and the mast cell degranulation. However, all systemic effects of neostigmine were abolished by cromolyn. The cholinergic agents or cromolyn did not alter basal release of CGRP, in vitro, but cromolyn alleviated the CGRP\u2010inducing effect of capsaicin while atropine failed to do it. These results ensure for a first time direct evidence that endogenous acetylcholine contributes to migraine pathology mainly by activating meningeal mast cells while muscarinic receptors are involved in CGRP release from trigeminal ganglion and brainstem, without excluding the possible role of nicotinic cholinergic receptors.<\/jats:p>","DOI":"10.1111\/ejn.15888","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T12:04:01Z","timestamp":1670587441000},"page":"2181-2192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Meningeal mast cell\u2010mediated mechanisms of cholinergic system modulation in neurogenic inflammation underlying the pathophysiology of migraine"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-2634","authenticated-orcid":false,"given":"Erkan","family":"Kilinc","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical School University of Bolu Abant Izzet Baysal  Bolu T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Ethem","family":"Torun","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School University of Bolu Abant Izzet Baysal  Bolu T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Baranoglu Kilinc","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Bolu Izzet Baysal State Hospital  Bolu T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411431333"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2009.01864.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102412439354"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013205"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102415597891"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12458"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221114773"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6614"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2005.01035.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.09.007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.03.004"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417748563"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1734-1140(12)70911-8"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002939"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12087.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2009.01924.x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516134113"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13529"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.10.004"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.129"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14897"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12915"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23523"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.12.024"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15145"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08774.x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00136"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.03.012"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01971484"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.5812\/aapm.42210"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116670"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.1997.1703166.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413502735"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01855-7"},{"key":"e_1_2_11_36_1","article-title":"Investigation of carbachol and PACAP38 in a human model of migraine","volume":"57","author":"Schytz H. 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