Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model

被引:11
作者
Arai, Takahito [1 ]
Suzuki-Narita, Miyako [2 ]
Takeuchi, Jun [3 ]
Tajiri, Ikuko [1 ]
Inage, Kazuhide [1 ]
Kawarai, Yuya [1 ]
Eguchi, Yawara [1 ]
Shiga, Yasuhiro [1 ]
Hozumi, Takashi [4 ]
Kim, Geundong [5 ]
Tsuchiya, Ryuto [1 ]
Otagiri, Takuma [1 ]
Mukaihata, Tomohito [1 ]
Hishiya, Takahisa [1 ]
Toshi, Noriyasu [1 ]
Okuyama, Kohei [1 ]
Tokeshi, Soichiro [1 ]
Furuya, Takeo [1 ]
Maki, Satoshi [1 ,6 ]
Matsuura, Yusuke [1 ]
Suzuki, Takane [2 ]
Nakamura, Junichi [1 ]
Hagiwara, Shigeo [1 ]
Ohtori, Seiji [1 ]
Orita, Sumihisa [1 ,6 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[2] Chiba Univ, Grad Sch Med, Dept Bioenvironm Med, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan
[3] Seikagaku Corp, Med Affairs Unit, Chiyoda Ku, 1-6-1 Marunouchi, Tokyo 1000005, Japan
[4] Kimitsu Chuo Hosp, Dept Orthopaed Surg, 1010 Sakurai, Kisarazu, Chiba 2928535, Japan
[5] Tokyo Metropolitan Bokutoh Hosp, Tertiary Emergency Med Ctr Trauma & Crit Care, Sumida Ku, 4-23-15 Kotobashi, Tokyo 1308575, Japan
[6] Chiba Univ, Ctr Frontier Med Engn, Inage Ku, 1-33 Yayoi Cho,CFME Room B201, Chiba 2638522, Japan
关键词
Diclofenac etalhyaluronate; Rat monoiodoacetate model; Osteoarthritis; Pain; GENE-RELATED PEPTIDE; DORSAL-ROOT GANGLIA; HIP OSTEOARTHRITIS; SUBCHONDRAL BONE; ARTICULAR-CARTILAGE; PERIPHERAL-NERVE; PAIN; IODOACETATE; JOINT; HYPERALGESIA;
D O I
10.1186/s12891-022-05937-y
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Background Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). Methods We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. Results Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. Conclusion DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.
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页数:10
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