{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:05:06Z","timestamp":1785236706335,"version":"3.55.0"},"reference-count":114,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["National Brain Research Program 2017-1.2.1-NKP-2017-00002"],"award-info":[{"award-number":["National Brain Research Program 2017-1.2.1-NKP-2017-00002"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00050"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["EFOP 3.6.2-17-2017-00008"],"award-info":[{"award-number":["EFOP 3.6.2-17-2017-00008"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Government of Hungary","doi-asserted-by":"publisher","award":["EFOP-3.6.1-16-2016-00004"],"award-info":[{"award-number":["EFOP-3.6.1-16-2016-00004"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Goverment of Hungary","award":["NTP-NFT\u00d6-18-B-0455"],"award-info":[{"award-number":["NTP-NFT\u00d6-18-B-0455"]}]},{"name":"National Research, Development and Innovation Office of Hungary","award":["OTKA FK132587"],"award-info":[{"award-number":["OTKA FK132587"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund\u2019s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-\/-) mice. Expression of the SGC\/astrocyte marker in the TG and TNC was significantly lower in intact and saline\/CFA-treated Tac4-\/- mice. The procedural stress-related increase of the SGC\/astrocyte marker was also strongly attenuated in Tac4-\/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-\/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.<\/jats:p>","DOI":"10.3390\/ijms21082938","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T02:10:52Z","timestamp":1587607852000},"page":"2938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization"],"prefix":"10.3390","volume":"21","author":[{"given":"Timea","family":"Acz\u00e9l","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9la","family":"Kecsk\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Kun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1lm\u00e1n","family":"Szenthe","sequence":"additional","affiliation":[{"name":"Carlsbad Research Organization Ltd, H-9244 \u00dajr\u00f3naf\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-523X","authenticated-orcid":false,"given":"Ferenc","family":"B\u00e1n\u00e1ti","sequence":"additional","affiliation":[{"name":"RT-Europe Ltd, H-9200 Mosonmagyar\u00f3v\u00e1r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Szathmary","sequence":"additional","affiliation":[{"name":"Galenbio Ltd, H-9200 Mosonmagyar\u00f3v\u00e1r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f3bert","family":"Herczeg","sequence":"additional","affiliation":[{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Urb\u00e1n","sequence":"additional","affiliation":[{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Gyenesei","sequence":"additional","affiliation":[{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-2732","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Gaszner","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of P\u00e9cs Medical School, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"PharmInVivo Ltd., H-7629 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kata","family":"B\u00f6lcskei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10194-019-1043-7","article-title":"Animal models of migraine and experimental techniques used to examine trigeminal sensory processing","volume":"20","author":"Harriott","year":"2019","journal-title":"J. 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