کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2722798 1566720 2016 19 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aconitum-Derived Bulleyaconitine A Exhibits Antihypersensitivity Through Direct Stimulating Dynorphin A Expression in Spinal Microglia
ترجمه فارسی عنوان
Bulleyaconitine A حاصل از آکونیتوم نشان دهنده حساسیت به آنتی اکسیدان ها از طریق تحریک مستقیم دینورفین بیان در Microglia نخاعی هستند
کلمات کلیدی
Bulleyaconitine A؛ ضد حساسیت؛ تحمل مورفین به ضددردی؛ میکروگلایی نخاعی؛ دینورفین A؛ کانال سدیم
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی


• Bulleyaconitine A (BAA) attenuates neuropathic, bone cancer, and formalin pain.
• BAA does not induce antinociceptive tolerance.
• Minocycline blocks BAA antiallodynia but not neurotoxicity.
• Bulleyaconitine A stimulates dynorphin A expression in spinal microglia.
• Dynorphin A antisera and κ-opioid receptor antagonist eliminate BAA antiallodynia.

Aconitine and its structurally-related diterpenoid alkaloids have been shown to interact differentially with neuronal voltage-dependent sodium channels, which was suggested to be responsible for their analgesia and toxicity. Bulleyaconitine A (BAA) is an aconitine analogue and has been prescribed for the management of pain. The present study aimed to evaluate the inhibitory effects of BAA on pain hypersensitivity and morphine antinociceptive tolerance, and explore whether the expression of dynorphin A in spinal microglia was responsible for its actions. Single intrathecal or subcutaneous (but not intraventricular or local) injection of BAA blocked spinal nerve ligation-induced painful neuropathy, bone cancer-induced pain, and formalin-induced tonic pain by 60 to 100% with the median effective dose values of 94 to 126 ng per rat (intrathecal) and 42 to 59 μg/kg (subcutaneous), respectively. After chronic treatment, BAA did not induce either self-tolerance to antinociception or cross-tolerance to morphine antinociception, and completely inhibited morphine tolerance. The microglial inhibitor minocycline entirely blocked spinal BAA (but not exogenous dynorphin A) antinociception, but failed to attenuate spinal BAA neurotoxicity. In a minocycline-sensitive and lidocaine- or ropivacaine-insensitive manner, BAA stimulated the expression of dynorphin A in the spinal cord, and primary cultures of microglia but not of neurons or astrocytes. The blockade effects of BAA on nociception and morphine tolerance were totally eliminated by the specific dynorphin A antiserum and/or κ-opioid receptor antagonist. Our results suggest that BAA eliminates pain hypersensitivity and morphine tolerance through directly stimulating dynorphin A expression in spinal microglia, which is not dependent on the interactions with sodium channels.PerspectiveThe newly illustrated mechanisms underlying BAA antinociception help us to better understand and develop novel dynorphin A expression-based painkillers to treat chronic pain.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Pain - Volume 17, Issue 5, May 2016, Pages 530–548
نویسندگان
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