{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:03:03Z","timestamp":1791205383538,"version":"4.1.0"},"reference-count":63,"publisher":"Society for Neuroscience","issue":"14","license":[{"start":{"date-parts":[[2005,10,6]],"date-time":"2005-10-06T00:00:00Z","timestamp":1128556800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2005,4,6]]},"abstract":"<jats:p>Opioid \u03bc- and \u03b4-receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and<jats:italic>in vivo<\/jats:italic>. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the \u03bc agonist [<jats:sc>d<\/jats:sc>-Ala<jats:sup>2<\/jats:sup>,<jats:italic>N<\/jats:italic>-Me-Phe<jats:sup>4<\/jats:sup>, Gly-ol<jats:sup>5<\/jats:sup>]-enkephalin (DAMGO) (1 \u03bc<jats:sc>m<\/jats:sc>) and decreased by the \u03b4 agonist [<jats:sc>d<\/jats:sc>-Phe<jats:sup>2,5<\/jats:sup>]-enkephalin (DPDPE) (1 \u03bc<jats:sc>m<\/jats:sc>).<jats:italic>In vivo<\/jats:italic>, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the \u03ba agonist<jats:italic>trans<\/jats:italic>-(1<jats:italic>S<\/jats:italic>,2<jats:italic>S<\/jats:italic>)-3,4-dichloro-<jats:italic>N<\/jats:italic>-mathyl-<jats:italic>N<\/jats:italic>-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the \u03bc and \u03b4 agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.<\/jats:p>","DOI":"10.1523\/jneurosci.0252-05.2005","type":"journal-article","created":{"date-parts":[[2005,4,6]],"date-time":"2005-04-06T19:43:18Z","timestamp":1112816598000},"page":"3651-3660","source":"Crossref","is-referenced-by-count":104,"title":["Inhibition by Spinal \u03bc- and \u03b4-Opioid Agonists of Afferent-Evoked Substance P Release"],"prefix":"10.1523","volume":"25","author":[{"given":"Ichiro","family":"Kondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos G.","family":"Marvizon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Salgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Codeluppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ying","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony L.","family":"Yaksh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2005,4,6]]},"reference":[{"key":"2023041303115757000_25.14.3651.1","doi-asserted-by":"crossref","first-page":"8049","DOI":"10.1523\/JNEUROSCI.17-20-08049.1997","volume":"17","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00317-7"},{"key":"2023041303115757000_25.14.3651.3","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(89)90003-X"},{"key":"2023041303115757000_25.14.3651.4","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.1523\/JNEUROSCI.17-15-05921.1997","volume":"17","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.5","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/jn.1999.81.3.1379","volume":"81","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303115757000_25.14.3651.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4637-03.2004"},{"key":"2023041303115757000_25.14.3651.7","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91519-M"},{"key":"2023041303115757000_25.14.3651.8","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198909001-00672"},{"key":"2023041303115757000_25.14.3651.9","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00492-1"},{"key":"2023041303115757000_25.14.3651.10","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00006-E"},{"key":"2023041303115757000_25.14.3651.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(97)00097-6"},{"key":"2023041303115757000_25.14.3651.12","doi-asserted-by":"publisher","DOI":"10.1038\/284351a0"},{"key":"2023041303115757000_25.14.3651.13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00501394"},{"key":"2023041303115757000_25.14.3651.14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1113\/jphysiol.1987.sp016731","volume":"391","year":"1987","journal-title":"J Physiol (Lond)"},{"key":"2023041303115757000_25.14.3651.15","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.1523\/JNEUROSCI.16-21-06975.1996","volume":"16","year":"1996","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.16","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1523\/JNEUROSCI.14-03-01646.1994","volume":"14","year":"1994","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.17","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1523\/JNEUROSCI.19-17-07670.1999","volume":"19","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.18","doi-asserted-by":"publisher","DOI":"10.1038\/268549a0"},{"key":"2023041303115757000_25.14.3651.19","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)91065-5"},{"key":"2023041303115757000_25.14.3651.20","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(96)00333-8"},{"key":"2023041303115757000_25.14.3651.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00501-3"},{"key":"2023041303115757000_25.14.3651.22","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90370-X"},{"key":"2023041303115757000_25.14.3651.23","doi-asserted-by":"publisher","DOI":"10.1038\/386721a0"},{"key":"2023041303115757000_25.14.3651.24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702260"},{"key":"2023041303115757000_25.14.3651.25","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93946-U"},{"key":"2023041303115757000_25.14.3651.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.7539937"},{"key":"2023041303115757000_25.14.3651.27","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5336.275"},{"key":"2023041303115757000_25.14.3651.28","doi-asserted-by":"crossref","first-page":"8129","DOI":"10.1523\/JNEUROSCI.17-21-08129.1997","volume":"17","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.29","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1097\/00001756-199908020-00020","volume":"10","year":"1999","journal-title":"NeuroReport"},{"key":"2023041303115757000_25.14.3651.30","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00445.x"},{"key":"2023041303115757000_25.14.3651.31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705578"},{"key":"2023041303115757000_25.14.3651.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00977-6"},{"key":"2023041303115757000_25.14.3651.33","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90019-5"},{"key":"2023041303115757000_25.14.3651.34","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200203000-00032"},{"key":"2023041303115757000_25.14.3651.35","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4179(89)90039-5"},{"key":"2023041303115757000_25.14.3651.36","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.1523\/JNEUROSCI.13-12-05228.1993","volume":"13","year":"1993","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00571-6"},{"key":"2023041303115757000_25.14.3651.38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1213\/00000539-199308000-00010","volume":"77","year":"1993","journal-title":"Anesth Analg"},{"key":"2023041303115757000_25.14.3651.39","doi-asserted-by":"crossref","first-page":"6483","DOI":"10.1523\/JNEUROSCI.17-16-06483.1997","volume":"17","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.40","first-page":"1","volume":"228","year":"1984","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303115757000_25.14.3651.41","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90117-I"},{"key":"2023041303115757000_25.14.3651.42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.787ba.x"},{"key":"2023041303115757000_25.14.3651.43","doi-asserted-by":"crossref","first-page":"9171","DOI":"10.1523\/JNEUROSCI.23-27-09171.2003","volume":"23","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.44","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.01969.x"},{"key":"2023041303115757000_25.14.3651.45","doi-asserted-by":"publisher","DOI":"10.1038\/nn966"},{"key":"2023041303115757000_25.14.3651.46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.42.092401.143905"},{"key":"2023041303115757000_25.14.3651.47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01969.x"},{"key":"2023041303115757000_25.14.3651.48","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(93)90045-T"},{"key":"2023041303115757000_25.14.3651.49","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1523\/JNEUROSCI.22-10-04103.2002","volume":"22","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1054\/jpai.2000.9806","volume":"1","year":"2000","journal-title":"Pain"},{"key":"2023041303115757000_25.14.3651.51","doi-asserted-by":"crossref","first-page":"9642","DOI":"10.1523\/JNEUROSCI.19-21-09642.1999","volume":"19","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.52","doi-asserted-by":"crossref","first-page":"8578","DOI":"10.1523\/JNEUROSCI.20-23-08578.2000","volume":"20","year":"2000","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.53","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1523\/JNEUROSCI.21-10-03656.2001","volume":"21","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303115757000_25.14.3651.54","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0028-3908(73)90081-6","volume":"12","year":"1973","journal-title":"Neuropharmacology"},{"key":"2023041303115757000_25.14.3651.55","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(81)90633-3"},{"key":"2023041303115757000_25.14.3651.56","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1399-6576.1997.tb04623.x","volume":"41","year":"1997","journal-title":"Acta Anaesthesiol Scand"},{"key":"2023041303115757000_25.14.3651.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(99)01370-X"},{"key":"2023041303115757000_25.14.3651.58","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(76)90029-9"},{"key":"2023041303115757000_25.14.3651.59","first-page":"411","volume":"202","year":"1977","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303115757000_25.14.3651.60","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(77)90145-2"},{"key":"2023041303115757000_25.14.3651.61","doi-asserted-by":"publisher","DOI":"10.1038\/286155a0"},{"key":"2023041303115757000_25.14.3651.62","first-page":"633","volume":"215","year":"1980","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303115757000_25.14.3651.63","doi-asserted-by":"publisher","DOI":"10.1038\/305529a0"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0252-05.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T16:42:17Z","timestamp":1681404137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0252-05.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,6]]},"references-count":63,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2005,4,6]]},"published-print":{"date-parts":[[2005,4,6]]}},"alternative-id":["10.1523\/JNEUROSCI.0252-05.2005"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0252-05.2005","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,6]]}}}