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However, the mechanisms underlying its analgesic effects remain unclear. This study aimed to determine the concentration of lidocaine that reaches target tissues after intranasal application and its impact on the excitability of trigeminal ganglion neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse model was used to examine lidocaine (10%) distribution after intranasal administration, employing liquid chromatography-mass spectrometry (LC-MS). Fluorescence calcium imaging with electrical field stimulation on acutely cultured murine trigeminal ganglion cells was applied to determine the effects of the pre-determined lidocaine concentrations on their excitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After intranasal application, lidocaine concentrations ranged from approximately 2.5 \u03bcM in plasma to 7 \u03bcM in trigeminal ganglia. Calcium imaging revealed that 100 \u03bcM lidocaine was required to decrease electrical responses in capsaicin-unresponsive trigeminal ganglion neurons. In capsaicin-responsive nociceptive neurons such an inhibition was already observed at 10 \u03bcM lidocaine and these neurons also displayed a sustained increase in calcium that failed to return to baseline levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that intracranial lidocaine concentrations after intranasal administration are sufficiently high to selectively affect depolarized trigeminal nociceptors with ongoing activity, providing a potential mechanism for the analgesic effects of intranasally applied lidocaine. These results have implications for the use of intranasal lidocaine as a treatment for headache.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024261453548","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:42:18Z","timestamp":1782312138000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distribution of intranasal lidocaine and its effect on electrically-evoked calcium signals in mouse trigeminal ganglion neurons"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2267-9754","authenticated-orcid":false,"given":"Lisa","family":"Tiebl","sequence":"first","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-3731","authenticated-orcid":false,"given":"Hans J\u00fcrgen","family":"Solinski","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Belejova","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Soares","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pitzer","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Palkovacs","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Poschet","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-7241","authenticated-orcid":false,"given":"Martin","family":"Schmelz","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Oehler","sequence":"additional","affiliation":[{"name":"University Medical Clinic Essen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8617-9133","authenticated-orcid":false,"given":"Richard","family":"Carr","sequence":"additional","affiliation":[{"name":"Heidelberg University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01402-2"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03612.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30322-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2025-085564"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/10600280231209439"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-9-S3-S5"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00101-020-00900-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11123296"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.1999.3908543.x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224285"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1985.04060050098017"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.1995.hed3502083.x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-003-0024-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2000.00026.x"},{"key":"e_1_3_4_16_2","first-page":"331","article-title":"Evaluation of efficacy of intra-nasal lidocaine for headache relief in patients refer to emergency department","volume":"19","author":"Mohammadkarimi N","year":"2014","unstructured":"Mohammadkarimi N, Jafari M, Mellat A, et al. 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