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Although NTS2 receptors play an important role in modulating the activity of spinal neurons, we have recently implicated NTS1 receptors in NT's analgesic effects in acute spinal pain paradigms. The current experiments were thus designed to examine the antinociceptive effects of intrathecal administration of NTS1 agonists in formalin\u2010induced tonic pain in rats. We first established, using immunoblotting and immunohistochemical approaches, that NTS1 receptors were present in small\u2010 and medium\u2010sized dorsal root ganglion cells and localized in the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal injection of NT (1\u201315\u2003\u03bcg\/kg) or NTS1 preferring agonists on the nocifensive response to intraplantar formalin. Both NTS1\u2010agonists, PD149163 (10\u2013120\u2003\u03bcg\/kg) and NT69L (1\u2013100\u2003\u03bcg\/kg), dose\u2010dependently attenuated the formalin\u2010induced behaviors. Accordingly, NTS1 agonists markedly suppressed pain\u2010evoked c\u2010<jats:italic>fos<\/jats:italic>expression in the superficial, nucleus proprius and neck regions of the spinal dorsal horn. The concomitant administration of PD149163 with the NTS1 antagonist SR48692 (3\u2003\u03bcg\/kg) significantly reversed PD149163\u2010induced antinociception, confirming the implication of NTS1 in tonic pain. In contrast, NT69L\u2019s analgesic effects were partly abolished by co\u2010administration of SR48692, indicating that NT69L\u2010induced effects may also be exerted through interaction with NTS2. These results demonstrate that NTS1 receptors play a key role in the mediation of the analgesic effects of NT in persistent pain and suggest that NTS1\u2010selective agonists may represent a new line of analgesic compounds.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.05205.x","type":"journal-article","created":{"date-parts":[[2008,2,26]],"date-time":"2008-02-26T13:20:46Z","timestamp":1204032046000},"page":"1100-1114","source":"Crossref","is-referenced-by-count":55,"title":["Spinal NTS1 receptors regulate nociceptive signaling in a rat formalin tonic pain model"],"prefix":"10.1111","volume":"105","author":[{"given":"Genevi\u00e8ve","family":"Roussy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc\u2010Andr\u00e9","family":"Dansereau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Dor\u00e9\u2010Savard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Belleville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Beaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott","family":"Richelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Sarret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90139-M"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-15-04733.1996"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)90619-X"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.12.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.12.031"},{"key":"e_1_2_7_7_1","article-title":"Neurotensin\u2010produced antinociception in the rostral ventromedial medulla is partially mediated by spinal cord norepinephrine","author":"Buhler A. 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