کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2532404 1559010 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of NCAM and FGF receptor signaling in the development of analgesic tolerance to morphine
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Involvement of NCAM and FGF receptor signaling in the development of analgesic tolerance to morphine
چکیده انگلیسی

This study examined the involvement of neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, in the development of tolerance to morphine. Furthermore, we focused on fibroblast growth factor (FGF) receptor and protein kinase C (PKC)-α as part of the intracellular signal transduction pathways underlying NCAM stimulation. The development of analgesic tolerance to morphine was gradually observed during daily treatment of morphine (10 mg/kg, s.c.) for 5 days. Morphine treatment gradually and significantly decreased the NCAM expression levels. However it returned to normal levels immediately after re-treatment of morphine. Treatment of AS-ODN against NCAM completely inhibited analgesic tolerance to morphine. Protein expression levels of PKC-α were significantly increased by repeated morphine treatment in a NCAM-AS-ODN-reversible manner. Interestingly, alterations of protein interactions between NCAM and FGF receptor were observed under repeated morphine treatment. In addition, SU5402 (2 μg/mouse, i.c.v.), an inhibitor of FGF receptor, completely abolished the development of analgesic tolerance to morphine. Furthermore, κ-opioid receptor stimulation using U-50,488 H, a κ-opioid receptor agonist, or establishment of formalin-induced chronic pain can completely suppress these changes in protein expression levels of NCAM and PKC-α and inhibit development of analgesic tolerance to morphine. These findings suggest that NCAM and its interaction with FGF receptor in the mechanism of up-regulation of PKC-α may contribute to the development of analgesic tolerance to morphine. Chronic pain or κ-opioid receptor stimulation could modulate these phenomena and suppress the development of analgesic tolerance to morphine.

The development of analgesic tolerance to morphine by repeated morphine treatment for 5 days was significantly suppressed by NCAM-AS-ODN treatment (A). The expression levels of NCAM in midbrain were varied in quantity during repeated morphine treatment (down-regulation and up-regulation) (B). This repeated morphine-induced “unsteady expression” of NCAM may be involved in the mechanism of the development of morphine tolerance.Figure optionsDownload high-quality image (127 K)Download as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 672, Issues 1–3, 15 December 2011, Pages 77–82
نویسندگان
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