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    KCI등재 SCOPUS SCIE

    Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats

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    https://www.riss.kr/link?id=A104327889

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    다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

    Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processingis generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in thenerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the changein 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in thecarrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppressesthe activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its rolein the carrageenan model has not been reported.
    Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Westernblotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine(5,7-DHT) on the expression of the phospho-ERK was measured.
    Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals.
    The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the levelof a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injectionin the animals treated with 5,7-DHT than in the naive and control rats.
    Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggestingthat the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in theexpression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhancedpain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.
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    Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processingis generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in thenerve injury model. ...

    Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processingis generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in thenerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the changein 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in thecarrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppressesthe activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its rolein the carrageenan model has not been reported.
    Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Westernblotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine(5,7-DHT) on the expression of the phospho-ERK was measured.
    Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals.
    The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the levelof a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injectionin the animals treated with 5,7-DHT than in the naive and control rats.
    Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggestingthat the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in theexpression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhancedpain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

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    참고문헌 (Reference)

    1 Oatway MA, "The 5-HT3 receptor facilitates at-level mechanical allodynia following spinal cord injury" 110 : 259-268, 2004

    2 Dogrul A, "Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord" 149 : 498-505, 2006

    3 Seyrek M, "Systemic cannabinoids produce CB(1)-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7)and 5-HT(2A)receptors" 649 : 183-194, 2010

    4 정신호, "Spinal Noradrenergic Modulation and the Role of the Alpha-2 Receptor in the Antinociceptive Effect of Intrathecal Nefopam in the Formalin Test" 대한통증학회 27 (27): 23-29, 2014

    5 Yanarates O, "Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, O-Desmethyltramadol, via activation of descending serotonergic pathways" 112 : 696-710, 2010

    6 Doly S, "Pre-and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord : immunocytochemical evidence" 490 : 256-269, 2005

    7 Brenchat A, "Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity" 149 : 483-494, 2010

    8 Ji RR, "Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity" 2 : 1114-1119, 1999

    9 Wei F, "Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain" 30 : 8624-8636, 2010

    10 Pearson G, "Mitogen-activated protein(MAP)kinase pathways : regulation and physiological functions" 22 : 153-183, 2001

    1 Oatway MA, "The 5-HT3 receptor facilitates at-level mechanical allodynia following spinal cord injury" 110 : 259-268, 2004

    2 Dogrul A, "Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord" 149 : 498-505, 2006

    3 Seyrek M, "Systemic cannabinoids produce CB(1)-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7)and 5-HT(2A)receptors" 649 : 183-194, 2010

    4 정신호, "Spinal Noradrenergic Modulation and the Role of the Alpha-2 Receptor in the Antinociceptive Effect of Intrathecal Nefopam in the Formalin Test" 대한통증학회 27 (27): 23-29, 2014

    5 Yanarates O, "Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, O-Desmethyltramadol, via activation of descending serotonergic pathways" 112 : 696-710, 2010

    6 Doly S, "Pre-and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord : immunocytochemical evidence" 490 : 256-269, 2005

    7 Brenchat A, "Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity" 149 : 483-494, 2010

    8 Ji RR, "Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity" 2 : 1114-1119, 1999

    9 Wei F, "Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain" 30 : 8624-8636, 2010

    10 Pearson G, "Mitogen-activated protein(MAP)kinase pathways : regulation and physiological functions" 22 : 153-183, 2001

    11 Karim F, "Metabotropic glutamate receptor subtypes 1 and 5 are activators of extracellular signal-regulated kinase signaling required for inflammatory pain in mice" 21 : 3771-3779, 2001

    12 Ji RR, "MAP kinase and pain" 60 : 135-148, 2009

    13 Sommer C, "Is serotonin hyperalgesic or analgesic?" 10 : 101-106, 2006

    14 Geranton SM, "Injury induced activation of extracellular signal-regulated kinase(ERK)in the rat rostral ventromedial medulla(RVM)is age dependant and requires the lamina I projection pathway" 6 : 54-, 2010

    15 Adwanikar H, "Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation" 111 : 125-135, 2004

    16 Viguier F, "GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7receptor activation in rats suffering from neuropathic pain" 63 : 1093-1106, 2012

    17 Galan A, "Extracellular signaling-regulated kinase-1 and-2(ERK 1/2)mediate referred hyperalgesia in a murine model of visceral pain" 116 : 126-134, 2003

    18 Bardin L, "Effect of intrathecal serotonin on nociception in rats : influence of the pain test used" 113 : 81-87, 1997

    19 Zhuang ZY, "ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model" 114 : 149-159, 2005

    20 Yang J, "Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending serotonergic modulation in inflammatory pain induced in formalin and carrageenan rat models" 113 : 138-147, 2014

    21 Svensson CI, "Descending serotonergic facilitation of spinal ERK activation and pain behavior" 580 : 6629-6634, 2006

    22 Rahman W, "Descending serotonergic facilitation mediated through rat spinal 5HT3 receptors is unaltered following carrageenan inflammation" 361 : 229-231, 2004

    23 Millan MJ., "Descending control of pain" 66 : 355-474, 2002

    24 Mason P., "Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions" 24 : 737-777, 2001

    25 Amaya-Castellanos E, "Blockade of 5-HT7receptors reduces tactile allodynia in the rat" 99 : 591-597, 2011

    26 Suzuki R, "Bad news from the brain : descending 5-HT pathways that control spinal pain processing" 25 : 613-617, 2004

    27 Galan A, "Activation of spinal extracellular signaling-regulated kinase-1 and-2 by intraplantar carrageenan in rodents" 322 : 37-40, 2002

    28 Song XS, "Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats" 26 : 789-798, 2005

    29 Imbe H, "Activation of ERK in the rostral ventromedial medulla is involved in hyperalgesia during peripheral inflammation" 1187 : 103-110, 2008

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