کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
915271 1473253 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of the cysteine protease cathepsin S in neuropathic hyperalgesia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Role of the cysteine protease cathepsin S in neuropathic hyperalgesia
چکیده انگلیسی

Using a gene expression analysis approach we found that the mRNA encoding the lysosomal cysteine protease cathepsin S (CatS) was up-regulated in rat dorsal root ganglia (DRG) following peripheral nerve injury. CatS protein was expressed in infiltrating macrophages in DRG and near the site of injury. At both sites CatS expression progressively increased from day 3 to day 14 after injury. In naïve rats, intraplantar injection of activated rat recombinant (rr) CatS (0.3, 1 μg/rat) induced a mechanical hyperalgesia that developed within half-an-hour, diminished by 3 h and was absent after 24 h. Activated rrCathepsin B (CatB) and non-activated rrCatS injected intraplantarly at the same or higher doses than activated rrCatS had no effect on rat nociceptive thresholds. In nerve-injured rats, mechanical hyperalgesia, but not allodynia, was significantly reversed for up to 3 h by systemic administration of a non-brain penetrant, irreversible CatS inhibitor (LHVS, 3–30 mg/kg s.c.). Depletion of peripheral macrophages by intravenous injection of liposome encapsulate clodronate (1 ml, 5 mg/ml) partially reduced established mechanical hyperalgesia but not allodynia, and abolished the anti-hyperalgesic effect of LHVS. Our results demonstrate a pro-nociceptive effect of CatS and indicate that endogenous CatS released by peripheral macrophages contributes to the maintenance of neuropathic hyperalgesia following nerve injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN - Volume 130, Issue 3, August 2007, Pages 225–234
نویسندگان
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