Low Affinity NGF Receptor (p75 Neurotrophin Receptor) Inhibitory Antibody Reduces Pain Behavior and CGRP Expression in DRG in the Mouse Sciatic Nerve Crush Model
Low Affinity NGF Receptor (p75 Neurotrophin Receptor) Inhibitory Antibody Reduces Pain Behavior and CGRP Expression in DRG in the Mouse Sciatic Nerve Crush Model
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DOI：
10.1002/jor.20986
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Takahashi, Kazuhisa
中科院分区：
文献类型：
--
作者：
Fukui, Yu;Ohtori, Seiji;Takahashi, Kazuhisa
神经生长因子（NGF）及其低亲和力受体p75神经营养因子受体（p75 NTR）是疼痛的重要介质。为了进一步探讨所涉及的机制，我们研究了在小鼠坐骨神经挤压模型中使用p75 NTR抑制剂对疼痛行为和神经肽如降钙素基因相关肽（CGRP）表达的抑制。在神经损伤模型中，应用150 μ g p75 NTR抑制性抗体或10 μ l盐水。假手术组坐骨神经不受损伤。2周后测定L5背根神经节（dorsal root ganglions，DRG）CGRP和p75 NTR的表达。两组神经损伤后均出现机械性痛觉超敏反应，假手术组无明显差异（p < 0 0 5）。与假手术组相比，损伤组L5背根节神经元CGRP和p75 NTR免疫反应性均明显增强，而p75 NTR抑制剂则使CGRP和p75 NTR的表达明显降低（p <001）。应用p75 NTR抑制性抗体对夹捏的坐骨神经抑制CGRP和p75 NTR表达和疼痛行为。(C)2009骨科研究学会出版，Wiley Periodicals，Inc J Orthop Res 28 279-282，2010。
Nerve growth factor (NGF) and its low-affinity receptor, p75 neurotrophin receptor (p75NTR), are important mediators of pain. To explore further the mechanisms involved, we examined suppression of pain behavior and expression of neuropeptides such as caletonin gene-related peptide (CGRP) using a p75NTR inhibitory, in a mouse sciatic nerve crush model. In the nerve-injured model, 150 mu g of a p75 NTR inhibitory antibody or 10 mu l of saline were applied. The sciatic nerve in the sham-operated group was uninjured. Mechanical allodynia was measured for 2 weeks CGRP and p75NTR expression in L5 dorsal root ganglions (DRGs) was examined immunohistochemically Mechanical allodynia was found in the two nerve injured groups, but not in the sham-operated group (p < 0 05). However, the magnitude of the mechanical allodynia was significantly decreased after application of p75 NTR inhibitory antibody (p < 0 05) CGRP and p75NTR immunoreactivity in the L5 DRG neurons was upregulated in the injured nerve groups compared with the sham-operated group, however, p75 NTR inhibitory decreased the CGRP and p75NTR expression (p < 0 01). Application of the p75 NTR inhibitory antibody to the pinched sciatic nerve suppressed CGRP and p75NTR expression and pain behaviour. (C) 2009 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 279-282, 2010.