Miyamoto Shuichi, Nakamura Junichi, Ohtori Seiji, Orita Sumihisa, Nakajima Takayuki, Omae Takanori, Hagiwara Shigeo, Takazawa Makoto, Suzuki Miyako, Suzuki Takane, Takahashi Kazuhisa
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-8677, Chiba, Japan.
J Orthop Res. 2017 Jul;35(7):1424-1430. doi: 10.1002/jor.23395. Epub 2017 Apr 17.
The principal aim of this study was to clarify the time course of pain-related behavior and pain-related sensory innervation in a rat model of hip osteoarthritis (OA) induced by intra-articular injection of mono-iodoacetate (MIA). Using 6-week-old male Sprague Dawley rats, 25 μl of sterile saline of 1% Fluoro-Gold solution (FG) (control group; n = 30) and 25 μl of sterile saline of 1% FG with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints. Gait function was evaluated using a CatWalk system after 7, 14, 28, 42, and 56 days (n = 5, respectively). Neurons in the dorsal root ganglion (DRG) between L1 and L5 were immunostained for calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3). Gait analysis revealed the mean six parameters of hind paws at all time points were significantly lower in the MIA group (p = 0.05). The number of CGRP-immunoreactive (-IR) DRG neurons was significantly increased on days 7, 14, 28, and 42 peaking at 14 days in the MIA group. By contrast, expression of ATF3-IR in FG-labeled DRG neurons was significantly increased on days 42 and 57. The FG-labeled DRG neurons were distributed between L1 and L5, mainly at the L4 level. Pain-related behavior indicated by gait disturbance was observed in a MIA model of hip OA in rat. Early elevation of CGRP expression and late expression of ATF-3 were demonstrated in DRG neurons, possibly reflecting inflammatory pain and neuropathic pain in hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1424-1430, 2017.
本研究的主要目的是阐明关节内注射单碘乙酸盐(MIA)诱导的大鼠髋骨关节炎(OA)模型中疼痛相关行为和疼痛相关感觉神经支配的时间进程。使用6周龄雄性Sprague Dawley大鼠,将25μl含1%荧光金溶液(FG)的无菌盐水(对照组;n = 30)和25μl含1% FG及2mg MIA的无菌盐水(MIA组;n = 30)注入右髋关节。在第7、14、28、42和56天使用CatWalk系统评估步态功能(每组n = 5)。对L1至L5背根神经节(DRG)中的神经元进行降钙素基因相关肽(CGRP)和激活转录因子3(ATF3)免疫染色。步态分析显示,在所有时间点,MIA组后爪的六个平均参数均显著降低(p = 0.05)。MIA组在第7、14、28和42天,CGRP免疫反应性(-IR)DRG神经元数量显著增加,在第14天达到峰值。相比之下,FG标记的DRG神经元中ATF3-IR的表达在第42和57天显著增加。FG标记的DRG神经元分布在L1至L5之间,主要在L4水平。在大鼠髋OA的MIA模型中观察到步态紊乱所表明的疼痛相关行为。DRG神经元中CGRP表达早期升高和ATF-3晚期表达,可能反映了髋OA中的炎性疼痛和神经性疼痛。© 2017骨科研究协会。由Wiley Periodicals, Inc.出版。《矫形外科研究杂志》35:1424 - 1430, 2017。