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Intrathecal administration of sigma-1 receptor agonists facilitates nociception: Involvement of a protein kinase C-dependent pathway

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dc.contributor.authorRoh, Dae-Hyun-
dc.contributor.authorKim, Hyun-Woo-
dc.contributor.authorYoon, Seo Yeon-
dc.contributor.authorSeo, Hyoung-Sig-
dc.contributor.authorKwon, Young-Bae-
dc.contributor.authorKim, Kee-Won-
dc.contributor.authorHan, Ho-Jae-
dc.contributor.authorBeitz, Alvin J.-
dc.contributor.authorLee, Jang-Hern-
dc.date.accessioned2009-09-03T22:31:43Z-
dc.date.available2009-09-03T22:31:43Z-
dc.date.issued2008-07-24-
dc.identifier.citationJ Neurosci Res 86:3644-3654en
dc.identifier.issn0360-4012 (print)-
dc.identifier.issn1097-4547 (online)-
dc.identifier.urihttps://hdl.handle.net/10371/8599-
dc.description.abstractSigma sites, originally proposed as opioid receptor subtypes, are currently thought to represent unique receptors with a specific pattern of drug selectivity, a well-established anatomical distribution and broad range of functional roles including potential involvement in nociceptive mechanisms. We have recently demonstrated that intrathecal (i.t.) treatment with a sigma-1 receptor antagonist reduced formalin-induced pain behavior. In the present study, we investigated the potential role of spinal sigma-1 receptor agonists in peripherally initiated nociception and attempted to elucidate intracellular signaling mechanisms associated with spinal cord sigma-1 receptor activation in mice. The i.t. injection of the sigma-1 receptor agonists PRE-084 (PRE) or carbetapentane (CAR) significantly decreased tail-flick latency (TFL) and increased the frequency of paw withdrawal responses to mechanical stimulation (von Frey filament, 0.6 g) as well as the amount of Fos expression in the spinal cord dorsal horn induced by noxious paw-pinch stimulation. These PRE- or CAR-induced facilitatory effects on nociception were significantly blocked by i.t. pretreatment with the sigma-1 receptor antagonist, BD-1047, the phospholipase C (PLC) inhibitor, U-73,122, the Ca2+-ATPase inhibitor, thapsigargin, and the protein kinase C (PKC) inhibitor, chelerythrine. Western blot analysis further revealed that i.t. PRE or CAR injection significantly increased pan-PKC as well as the PKC, , and isoforms in the dorsal horn. Collectively, these findings demonstrate that calcium-dependent second messenger cascades including PKC are involved in the facilitation of nociception associated with spinal sigma-1 receptor activation.en
dc.description.sponsorshipBasic Research Program of the Korea Science
and Engineering Foundation; Contract grant number: R01-2005-000-
10580-0; Contract grant sponsor: Brain Research Center of the 21st
Century Frontier Research Program, funded by the Ministry of Science
and Technology of the Republic of Korea; Contract grant number:
M103KV010016 07K2201 01610.
en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.subjectpainen
dc.subjectprotein kinase Cen
dc.subjectphospholipase Cen
dc.subjectFos proteinen
dc.subjectsigma-1 receptoren
dc.titleIntrathecal administration of sigma-1 receptor agonists facilitates nociception: Involvement of a protein kinase C-dependent pathwayen
dc.typeArticleen
dc.contributor.AlternativeAuthor노대현-
dc.contributor.AlternativeAuthor김현우-
dc.contributor.AlternativeAuthor윤서연-
dc.contributor.AlternativeAuthor서형식-
dc.contributor.AlternativeAuthor권영배-
dc.contributor.AlternativeAuthor김기원-
dc.contributor.AlternativeAuthor한호재-
dc.contributor.AlternativeAuthor이장헌-
dc.identifier.doi10.1002/jnr.21802-
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