Objectives

Nerve growth factor (NGF) and sensory nerves are key factors in established osteoarthritis (OA) knee pain. We investigated the time course of NGF expression and sensory nerve growth across early and late stages of OA progression in rat knees.

Design

Knee OA was induced by medial meniscectomy in rats. OA histopathology, NGF expression, and calcitonin gene-related peptide immunoreactive (CGRP-IR) nerves were quantified pre-surgery and post-surgery at weeks 1, 2, 4 and 6. Pain-related behavior was evaluated using dynamic weight distribution and mechanical sensitivity of the hind paw.

Results

NGF expression in chondrocytes increased from week 1 and remained elevated until the advanced stage. In synovium, NGF expression increased only in early stages, whereas in osteochondral channels and bone marrow, NGF expression increased in the later stages of OA progression. CGRP-IR nerve density in suprapatellar pouch peaked at week 4 and decreased at week 6, whereas in osteochondral channels and bone marrow, CGRP-IR innervation increased through week 6. Percent ipsilateral weight-bearing decreased throughout the OA time course, whereas reduced paw withdrawal thresholds were observed only in later stages.

Conclusion

During progression of knee OA, time-dependent alterations of NGF expression and CGRP-IR sensory innervation are knee tissue specific. NGF expression increased in early stages and decreased in advanced stage in the synovium but continued to increase in osteochondral channels and bone marrow. Increases in CGRP- IR sensory innervation followed increases in NGF expression, implicating that NGF is a key driver of articular nerve growth associated with OA pain.

中文翻译：

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大鼠膝骨关节炎进展过程中神经生长因子表达和感觉神经生长的时程和定位

目标

神经生长因子 (NGF) 和感觉神经是确定的骨关节炎 (OA) 膝痛的关键因素。我们研究了大鼠膝关节 OA 进展早期和晚期 NGF 表达和感觉神经生长的时间进程。

设计

大鼠内侧半月板切除术诱发膝关节 OA。在手术前和手术后第 1、2、4 和 6 周对 OA 组织病理学、NGF 表达和降钙素基因相关肽免疫反应 (CGRP-IR) 神经进行量化。使用动态重量分布和力学评估疼痛相关行为后爪的敏感性。

结果

软骨细胞中的 NGF 表达从第 1 周开始增加，并保持升高直至晚期。在滑膜中，NGF 表达仅在早期阶段增加，而在骨软骨通道和骨髓中，NGF 表达在 OA 进展的后期阶段增加。髌上囊中的 CGRP-IR 神经密度在第 4 周达到峰值并在第 6 周下降，而在骨软骨通道和骨髓中，CGRP-IR 神经支配在第 6 周内增加。同侧负重百分比在整个 OA 时间过程中下降，而爪子减少退出阈值仅在后期阶段观察到。

结论

在膝关节 OA 的进展过程中，NGF 表达和 CGRP-IR 感觉神经支配的时间依赖性改变是膝关节组织特异性的。NGF表达在滑膜中早期增加，晚期减少，但在骨软骨通道和骨髓中继续增加。CGRP-IR 感觉神经支配的增加伴随着 NGF 表达的增加，表明 NGF 是与 OA 疼痛相关的关节神经生长的关键驱动因素。