Kawarai Yuya, Orita Sumihisa, Nakamura Junichi, Miyamoto Shuichi, Suzuki Miyako, Inage Kazuhide, Hagiwara Shigeo, Suzuki Takane, Nakajima Takayuki, Akazawa Tsutomu, Ohtori Seiji
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
Department of Orthopaedic Surgery, Kimitsu Chuo Hospital 1010 Sakurai, Kisarazu City, Chiba 292-8535, Japan.
J Orthop Res. 2018 Nov;36(11):2978-2986. doi: 10.1002/jor.24065. Epub 2018 Jul 13.
The aim of this study was to investigate the local production of proinflammatory cytokines, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy-five Sprague-Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N = 25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF-α, immunoreactive (-ir) neurons for calcitonin gene-related peptide (CGRP), and growth associated protein-43 (GAP-43) in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule-1 (Iba-1) in the dorsal horn of spinal cord, on post-induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point). For post-induction days 7-42, the MIA group presented significantly elevated concentrations of TNF-α than the other groups (p < 0.01), and a higher expression of CGRP-ir in FG-labeled DRG neurons than the sham group (p < 0.01). MIA rats also presented significantly more FG-labeled GAP-43-ir DRG neurons than the sham group on post-induction days 28, 42, and 56 (p < 0.05), and a significantly higher number of Iba-1-ir microglia in the ipsilateral dorsal horn than the other groups, on post-induction days 28, 42, and 56. The results suggest that in rat models, pain-related pathologies due to MIA-induced hip OA, originate from inflammation caused by cytokines, which leads to progressive, chronic neuronal damage that may cause neuropathic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2978-2986, 2018.
本研究旨在调查诱导性髋骨关节炎（OA）大鼠模型中促炎细胞因子的局部产生、背根神经节（DRG）与疼痛相关的感觉神经支配以及脊髓变化。使用了75只Sprague-Dawley大鼠，其中25只为对照组，50只注射到右髋关节（假手术组，注射25μl无菌生理盐水：N = 25；碘乙酸钠（MIA）组，注射25μl含2mg MIA的无菌生理盐水：N = 25）。在诱导后第7、14、28、42和56天（每组/每个时间点N = 5只大鼠），我们测量了DRG中肿瘤坏死因子-α（TNF-α）的局部产生、降钙素基因相关肽（CGRP）免疫反应性（-ir）神经元、生长相关蛋白43（GAP-43），以及脊髓背角中离子钙结合衔接分子1（Iba-1）免疫反应性神经元。在诱导后第7 - 42天，MIA组的TNF-α浓度显著高于其他组（p < 0.01），且在FG标记的DRG神经元中CGRP-ir的表达高于假手术组（p < 0.01）。在诱导后第28、42和56天，MIA大鼠的FG标记的GAP-43-ir DRG神经元也显著多于假手术组（p < 0.05），并且在诱导后第28、42和56天，同侧背角中Iba-1-ir小胶质细胞的数量显著多于其他组。结果表明，在大鼠模型中，MIA诱导的髋OA所致的疼痛相关病理变化源于细胞因子引起的炎症，这会导致进行性慢性神经元损伤，可能引发神经性疼痛。© 2018骨科研究协会。由Wiley Periodicals, Inc.出版。《矫形外科学研究》36:2978 - 2986, 2018。
