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Regulation der spinalen Expression von Nociceptin unter neuropathischen Schmerzen

Regulation of spinal nociceptin expression by neuropathic pain

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Zusammenfassung

Nociceptin ist der endogene Ligand eines neuen Opioidrezeptors, des „opioid receptor-like-1 receptor“ (ORL1-Rezeptor). Chronische inflammatorische Schmerzen gehen mit einer Steigerung der Expression von Nociceptin und dem ORL1-Rezeptor im Hinterhorn des Rückenmarks der Ratte einher; dies weist auf eine Beteiligung des endogenen Nociceptin-ORL1-Systems an der Genese pathologischer Schmerzzustände hin. In der vorliegenden Studie wird der Einfluss neuropathischer Schmerzen auf die Nociceptin-Expression mithilfe der Immunhistochemie untersucht. Zur Induktion neuropathischer Schmerzen wurde der N. ischiadicus bei 12 Ratten in Allgemeinanästhesie ligiert. Bei den 12 Ratten der Kontrollgruppe wurde eine Scheinoperation durchgeführt. Die Nervenligatur führte zu einer signifikanten thermischen Hyperalgesie auf der ipsilateralen Seite, einem typischen Zeichen neuropathischer Schmerzen; die Pfotenrückzugslatenz war an Tag 5 um 45,7±4,9% (p<0,05) und an Tag 10 um 37,3±1,8% (p<0,05) vermindert. Obwohl die Hyperalgesie bereits nach 5 Tagen voll ausgeprägt war, ließen sich zu diesem Zeitpunkt noch keine Veränderungen der Nociceptin-Expression im lumbalen Rückenmark feststellen. Zehn Tage nach Nervenligatur fand sich ein 2,46±0,38facher (p<0,05) bilateraler Anstieg der Nociceptin-Expression in den Laminae superficiales (I--II) im Hinterhorn des Rückenmarks im Segment L4. Die genauen funktionellen Zusammenhänge zwischen neuropathischen Schmerzen, dem Nociceptin-ORL1-Rezeptor-System und potenziellen Therapiestrategien müssen in weiteren Experimenten untersucht werden.

Abstract

Nociceptin is the endogenous ligand of a new opioid receptor, the opioid receptor-like-1 (ORL1) receptor. Chronic inflammatory pain causes an increase in the expression of nociceptin and the ORL1 receptor in the dorsal horn of rat spinal cord, thus indicating an involvement of the endogenous nociceptin/ORL1 system in mechanisms of pathological pain. This study investigates the influence of neuropathic pain on the expression of nociceptin using immunohistochemistry. To induce neuropathic pain, a ligation of the sciatic nerve was performed in 12 rats under general anesthesia. A sham operation was performed in 12 rats of the control group. Nerve ligation caused a significant ipsilateral thermal hyperalgesia, a typical sign of neuropathic pain. The paw withdrawal latency was decreased by 45.7±4.9% (p<0.05) at day 5 and by 37.3±1.8% (p<0.05) at day 10. Although hyperalgesia was fully present after 5 days, no changes in nociceptin immunoreactivity in the lumbar spinal cord were detected at this time point. Ten days after nerve ligation, there was a 2.46±0.38 fold (p<0.05) bilateral increase in nociceptin immunoreactivity in the lamina superficiales (I and II), with a notable increase in the inner lamina II at the level of L4. Further investigations are necessary to elucidate the relationship between neuropathic pain, the nociceptin-ORL1 receptor system and potential therapeutic options.

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Danksagung

Die Untersuchung wurde durch den NIH grant AR 45570 (P. Pierce Palmer) finanziert. T. Meuser und C. Pietruck wurden durch das Köln Fortune Programm der Medizinischen Fakultät der Universität zu Köln und S. Grond durch das Wilhelm-Roux-Programm FKZ 6/06 der Martin-Luther-Universität Halle-Wittenberg unterstützt.

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Authors and Affiliations

  1. Klinik für Anästhesiologie und Operative Intensivmedizin, Universität zu Köln

    A. Gabriel, C. Pietruck & T. Meuser

  2. Department of Anesthesia, University of California San Francisco, San Francisco, USA

    M. Sharma & P. Pierce Palmer

  3. Klinik für Anästhesiologie und Operative Intensivmedizin, Martin-Luther-Universität Halle-Wittenberg

    S. Grond

  4. Klinik für Anästhesiologie und Operative Intensivmedizin, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle

    S. Grond

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  1. A. Gabriel
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  2. C. Pietruck
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  3. T. Meuser
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  4. M. Sharma
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  5. P. Pierce Palmer
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  6. S. Grond
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Correspondence to S. Grond.

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Gabriel, A., Pietruck, C., Meuser, T. et al. Regulation der spinalen Expression von Nociceptin unter neuropathischen Schmerzen. Anaesthesist 53, 621–628 (2004). https://doi.org/10.1007/s00101-004-0688-y

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