Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
J Orthop Res. 2010 Mar;28(3):279-83. doi: 10.1002/jor.20986.
Nerve growth factor (NGF) and its low-affinity receptor, p75 neurotrophin receptor (p75 NTR), are important mediators of pain. To explore further the mechanisms involved, we examined suppression of pain behavior and expression of neuropeptides such as calcitonin gene-related peptide (CGRP) using a p75 NTR inhibitory antibody, in a mouse sciatic nerve crush model. In the nerve-injured model, 150 microg of a p75 NTR inhibitory antibody or 10 microl of saline were applied. The sciatic nerve in the sham-operated group was uninjured. Mechanical allodynia was measured for 2 weeks. CGRP and p75 NTR 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 p75 NTR immunoreactivity in the L5 DRG neurons was upregulated in the injured nerve groups compared with the sham-operated group; however, p75 NTR inhibitory antibody decreased the CGRP and p75 NTR expression (p < 0.01). Application of the p75 NTR inhibitory antibody to the pinched sciatic nerve suppressed CGRP and p75 NTR expression and pain behavior.
神经生长因子（NGF）及其低亲和力受体 p75 神经营养素受体（p75NTR）是疼痛的重要介质。为了进一步探讨涉及的机制，我们使用 p75NTR 抑制性抗体在小鼠坐骨神经挤压模型中检查了疼痛行为的抑制和降钙素基因相关肽（CGRP）等神经肽的表达。在神经损伤模型中，应用 150μg p75NTR 抑制性抗体或 10μl 生理盐水。假手术组的坐骨神经未受伤。测量了 2 周的机械性痛觉过敏。免疫组织化学检查 L5 背根神经节（DRG）中的 CGRP 和 p75NTR 表达。在两个神经损伤组中发现了机械性痛觉过敏，但在假手术组中没有（p<0.05）。然而，应用 p75NTR 抑制性抗体后，机械性痛觉过敏的程度明显降低（p<0.05）。与假手术组相比，损伤神经组的 L5DRG 神经元中的 CGRP 和 p75NTR 免疫反应性上调；然而，p75NTR 抑制性抗体降低了 CGRP 和 p75NTR 的表达（p<0.01）。将 p75NTR 抑制性抗体应用于挤压的坐骨神经可抑制 CGRP 和 p75NTR 的表达和疼痛行为。
