{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:31:25Z","timestamp":1792611085814,"version":"4.5.0"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"The National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["DE018661"],"award-info":[{"award-number":["DE018661"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"The National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["DE023090"],"award-info":[{"award-number":["DE023090"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    A\u03b2-afferents are traditionally believed to be low-threshold mechanoreceptors (LTMRs) involved in sensing innocuous mechanical stimuli such as gentle touch; however, emerging evidence indicates that a subset of A\u03b2-afferents functions as high-threshold mechanoreceptors (HTMRs) involved in mechanical pain and termed A\u03b2-afferent nociceptors. While cooling is known to usually suppress neuronal excitability, its effects on the excitability of A\u03b2-afferent nociceptors remain unclear. Here, we used Nav1.8\n                    <jats:sup>ChR2\/eYFP<\/jats:sup>\n                    mice and patch-clamp recordings to examine how cooling affects intrinsic membrane properties, excitability, and ionic currents in A\u03b2-afferent nociceptors in the trigeminal ganglia (TG). A\u03b2-afferent nociceptors were identified as Nav1.8-positive (eYFP-positive) large-diameter (34\u201343 \u03bcm) TG neurons with their axon conduction velocities &gt;13 m\/s at 33\u00b0C. Cooling from 33 to 10\u00b0C progressively reduced axon conduction velocity and increased their stimulation threshold. However, at the soma of A\u03b2-afferent nociceptors, cooling decreased the action potential (AP) rheobase, increased AP amplitude and input resistance, and depolarized the resting membrane potential, although it increased the AP threshold and width. Voltage-clamp recordings showed that cooling suppressed both inward Na\n                    <jats:sup>+<\/jats:sup>\n                    and outward K\n                    <jats:sup>+<\/jats:sup>\n                    currents at the soma. Interestingly, the cooling-induced reduction in outward K\n                    <jats:sup>+<\/jats:sup>\n                    currents was largely mediated by temperature-sensitive two-pore-domain potassium (K2P) channels at the soma, suggesting a role in shifting intrinsic membrane properties toward increased excitability. Enhancing intrinsic membrane excitability at the soma of A\u03b2-afferent nociceptors raises the possibility that cooling may similarly affect excitability at their endings.\n                  <\/jats:p>","DOI":"10.1177\/17448069261463365","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:48:26Z","timestamp":1781869706000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of cooling on the excitability of trigeminal A\u03b2-afferent nociceptors in mice: Involvement of temperature-sensitive K2P channels"],"prefix":"10.1177","volume":"22","author":[{"given":"Amit Raj","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8404-9850","authenticated-orcid":false,"given":"Jianguo","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.07.015"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00489-x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.05.008"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/17448069221148958"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-023-01015-z"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/17448069241240452"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.2.629"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0828"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05880"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00652-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2203-07.2007"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00796.2015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13511"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1634-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2009"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2117"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-025-03089-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.06.017"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.872760"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1949.sp004388"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07839.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-32-10338.2003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.08.042"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2148"}],"container-title":["Molecular 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