کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6273514 | 1614801 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Autophagy in superficial spinal dorsal horn accelerates the cathepsin B-dependent morphine antinociceptive tolerance
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کلمات کلیدی
PFACatB3MAGADHRPPBSNF-κBEPSC - EPSCoRglutamic acid decarboxylase - glutamic acid dearboxylaseROS - ROSAutophagy - اتوفاژیImmunofluorescence - ایمونوفلورسانسGABAergic interneuron - اینترنئورون GABAergicdisinhibition - بازداری زدایی، مهارگسیختگیanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceexcitatory postsynaptic current - جریان پستیینپتیک تحریک کنندهmicrotubule-associated protein light chain 3 - زنجیره سبک پروتئینی مرتبط با میکروتوبول 3nuclear factor κB - فاکتور هسته ای κBPhosphate buffered saline - فسفات بافر شورMicroglia - میکروگلیاهاparaformaldehyde - پارافرمالدهیدHorseradish peroxidase - پراکسیداز هوررادیشCathepsin B - کاتئفسین BReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Opioids are the most widely used analgesics in the treatment of severe acute and chronic pain. However, opioids have many adverse side effects, including the development of antinociceptive tolerance after long-term use. The antinociceptive tolerance of opioids has limited their clinical use. A recent study has reported that autophagy is responsible for morphine-induced neuronal injury. However, little is known about the role of autophagy in morphine antinociceptive tolerance. In the present study, chronic morphine administration was found to induce the expression of autophagy-related proteins, including Beclin1 and microtubule-associated protein light chain 3 (LC3)-II, in GABAergic interneurons in the superficial layer (lamina I-II) of the spinal cord. A single intrathecal administration of autophagy inhibitors, 3-methyladenine (3MA) or wortmannin, inhibited the development of antinociceptive tolerance in a dose-dependent manner. Autophagy in the lamina I-II neurons was associated with increased level of cathepsin B (CatB), a lysosomal cysteine protease. The pharmacological blockade or gene deletion of CatB markedly prevented the development of morphine antinociceptive tolerance. Furthermore, the intrathecal administration of 3MA suppressed the upregulation of CatB 5Â days after morphine administration. Finally, CatB deficiency inhibited the increased release probability of glutamate in the lamina I neurons after chronic morphine treatment. These observations suggest that the dysfunction of the spinal GABAergic system induced by CatB-dependent excessive autophagy is partly responsible for morphine antinociceptive tolerance following chronic treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 275, 5 September 2014, Pages 384-394
Journal: Neuroscience - Volume 275, 5 September 2014, Pages 384-394
نویسندگان
Y. Hayashi, Y. Koga, X. Zhang, C. Peters, Y. Yanagawa, Z. Wu, T. Yokoyama, H. Nakanishi,