{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:25:01Z","timestamp":1791473101594,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["\u2116 20\u201015\u201000100"],"award-info":[{"award-number":["\u2116 20\u201015\u201000100"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Investigation of chronic homocysteine action on the excitability and N\u2010methyl\u2010D\u2010aspartate (NMDA) sensitivity of the peripheral trigeminovascular system of rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a neurological disease that affects 15%\u201320% of the general population. Epidemiological observations show that an increase of the sulfur\u2010containing amino acid homocysteine in plasma\u2014called hyperhomocysteinemia\u2014is associated with a high risk of migraine, especially migraine with aura. In animal studies, rats with hyperhomocysteinemia demonstrated mechanical allodynia, photophobia, and anxiety, and higher sensitivity to cortical spreading depression. In addition, rats with hyperhomocysteinemia were more sensitive in a model of chronic migraine induced by nitroglycerin which indicated the involvement of peripheral nociceptive mechanisms. The present work aimed to analyze the excitability of meningeal afferents and neurons isolated from the trigeminal ganglion of rats with prenatal hyperhomocysteinemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Experiments were performed on male rats born from females fed with a methionine\u2010rich diet before and during pregnancy. The activity of meningeal afferents was recorded extracellularly in hemiskull preparations ex\u00a0vivo and action potentials were characterized using cluster analysis. The excitability of trigeminal ganglion neurons was assessed using whole\u2010cell patch clamp recording techniques and calcium imaging studies. Meningeal mast cells were stained using toluidine blue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The baseline extracellular recorded electrical activity of the trigeminal nerve was higher in the hyperhomocysteinemia group with larger amplitude action potentials. Lower concentrations of KCl caused an increase in the frequency of action potentials of trigeminal afferents recorded in rat hemiskull ex\u00a0vivo preparations. In trigeminal ganglion neurons of rats with hyperhomocysteinemia, the current required to elicit at least one action potential (rheobase) was lower, and more action potentials were induced in response to stimulus of 2 \u00d7 rheobase. In controls, short\u2010term application of homocysteine and its derivatives increased the frequency of action potentials of the trigeminal nerve and induced Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients in neurons, which are associated with the activation of NMDA receptors. At the same time, in rats with hyperhomocysteinemia, we did not observe an increased response of the trigeminal nerve to NMDA. Similarly, the parameters of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients induced by NMDA, homocysteine, and its derivatives were not changed in rats with hyperhomocysteinemia. Acute incubation of the meninges in homocysteine and homocysteinic acid did not change the state of the mast cells, whereas in the model of hyperhomocysteinemia, an increased degranulation of mast cells in the meninges was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrated higher excitability of the trigeminal system of rats with hyperhomocysteinemia. Together with our previous finding about the lower threshold of generation of cortical spreading depression in rats with hyperhomocysteinemia, the present data provide evidence of homocysteine as a factor that increases the sensitivity of the peripheral migraine mechanisms, and the control of homocysteine level may be an important strategy for reducing the risk and\/or severity of migraine headache attacks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14710","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:29:39Z","timestamp":1713832179000},"page":"533-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia"],"prefix":"10.1111","volume":"64","author":[{"given":"Elizaveta","family":"Ermakova","sequence":"first","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Shaidullova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Gafurov","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alsu","family":"Kabirova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinara","family":"Nurmieva","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5412-2204","authenticated-orcid":false,"given":"Guzel","family":"Sitdikova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Department of Human and Animal Physiology Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413485658"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1129-2377-16-S1-A113"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-017-0742-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-009-1756-y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70090-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1983.0028"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90253-K"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2006.00485.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.03.012"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.12.004"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00195"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.12.005"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0255-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000437098"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207698"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-018-1016-4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17101733"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.01143.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01141.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-008-0917-2"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.11.065"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2009.01484.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13892"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2006.01107.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13540"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1074857"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040867"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065334"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113324"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12050735"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12615"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2746873"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10070995"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00226"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00266"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087519"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00287"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1129-2377-14-2"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000850"},{"key":"e_1_2_11_42_1","first-page":"70","article-title":"Method for simultaneous visualization of mast cells and nerve terminals in the rodent thymus","volume":"145","author":"Gusel'nikova VV","year":"2014","journal-title":"Morfologiia"},{"issue":"1","key":"e_1_2_11_43_1","article-title":"Parasympathetic cholinergic and peptidergic mechanisms of trigeminal pain","volume":"7","author":"Mikhailov N","year":"2017","journal-title":"Anesth Pain Med"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11055-020-00983-2"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/35093019"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3456"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0022093022030243"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6870"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00809.2012"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00246"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031529"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0216-y"},{"key":"e_1_2_11_53_1","first-page":"1804","article-title":"Comparative study on homocysteine levels in migraine patients and normal peoples","volume":"3","author":"Gavgani SC","year":"2012","journal-title":"Ann Biol Res"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.02.028"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0511-10.2010"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.91339.2008"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01567-4"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01443-7"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0769-2"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12381"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.10.051"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001669"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121953"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.04.040"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12371"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00029.2002"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-10-04511.1993"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.11.031"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.999509"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01229-3"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-018-2579-4"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-015-0564-y"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06207.x"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101441"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90339-9"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/386721a0"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X11311050002"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00136"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(10)80017-4"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:20:45Z","timestamp":1762078845000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":78,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/head.14710"],"URL":"https:\/\/doi.org\/10.1111\/head.14710","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,22]]},"assertion":[{"value":"2023-08-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}