{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T19:58:04Z","timestamp":1762113484718},"reference-count":44,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 \u03bcM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1\u2212 ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1\u2212 inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents.<\/jats:p>","DOI":"10.1152\/jn.00316.2014","type":"journal-article","created":{"date-parts":[[2014,9,4]],"date-time":"2014-09-04T15:03:24Z","timestamp":1409843004000},"page":"2697-2706","source":"Crossref","is-referenced-by-count":13,"title":["External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1"],"prefix":"10.1152","volume":"112","author":[{"given":"Mackenzie E.","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tally M.","family":"Largent-Milnes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Fawley","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1989.257.1.H79"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00398.2012"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5176-05.2006"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature06191"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705363"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2804-12.2013"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1299-11.2011"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.02.009"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2102"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.5.2213"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0315-14.2014"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00476.2011"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.211482"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0753-04.2004"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.01.004"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.02.016"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3982-10.2010"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00912.2013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000270758.77314.b4"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029395"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3491-09.2009"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.73.2.872"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1897"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.06.017"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00770-1"},{"key":"B26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00441-002-0682-0","volume":"311","author":"Patterson LM","year":"2003","journal-title":"Cell Tissue Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025015"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.017"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.08.010"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00012.2013"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11839"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/science.8085162"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181a9160e"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.71.6.2338"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019817"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.78.6.3198"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318260de41"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0090-04.2004"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2557-10.2010"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2009.10.003"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32832d2219"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.3.2120"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/7225"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00396.2009"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00316.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T01:53:52Z","timestamp":1598234032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00316.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,1]]},"references-count":44,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,12,1]]}},"alternative-id":["10.1152\/jn.00316.2014"],"URL":"https:\/\/doi.org\/10.1152\/jn.00316.2014","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,1]]}}}