کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9721045 | 1473270 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Pain sensitivity reflects a balance between pain facilitatory and inhibitory systems. To characterize the relationships between these systems we examined the interactions between the analgesic effects of morphine and the anti-analgesic effects of the pro-inflammatory cytokine interleukin-1 (IL-1). We report that administration of a neutral dose of IL-1β abolished morphine analgesia in mice, whereas acute or chronic blockade of IL-1 signaling by various IL-1 blockers (IL-1 receptor antagonist (IL-1ra), α-melanocyte-stimulating hormone, or IL-1 tri-peptide antagonist) significantly prolonged and potentiated morphine analgesia. Morphine-induced analgesia was also extended in strains of mice genetically impaired in IL-1 signaling (mice with transgenic over-expression of IL-1 receptor antagonist, deletion of the IL-1 receptor type I, or deletion of the IL-1 receptor accessory protein). The finding that IL-1 produces a marked anti-analgesic effect, suggests that it may also be involved in the development of opiate tolerance. Indeed, genetic or pharmacological blockade of IL-1 signaling prevented the development of tolerance following repeated morphine administration. Moreover, acute administration of IL-1ra in wild type mice, either immediately following the cessation of acute morphine analgesia, or following the development of chronic morphine tolerance, re-instated the analgesia, suggesting that blockade of the IL-1 system unmasks the analgesic effect of morphine. These findings suggest that morphine produces an IL-1-mediated homeostatic response, which serves to limit the duration and extent of morphine analgesia and which underlies the development of tolerance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pain - Volume 115, Issues 1â2, May 2005, Pages 50-59
Journal: Pain - Volume 115, Issues 1â2, May 2005, Pages 50-59
نویسندگان
Yehuda Shavit, Gilly Wolf, Inbal Goshen, Dina Livshits, Raz Yirmiya,