J-S An1, K Tsuji2, H Onuma3, N Araya4, M Isono5, T Hoshino6, K Inomata7, J Hino8, M Miyazato9, H Hosoda10, K Kangawa11, Y Nakagawa12, H Katagiri13, K Miyatake14, I Sekiya15, T Muneta16, H Koga17. 1. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: an.orj@tmd.ac.jp. 2. Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: tsuji.orj@tmd.ac.jp. 3. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: onuma.orj@tmd.ac.jp. 4. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: araya.orj@tmd.ac.jp. 5. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: iso.orth@tmd.ac.jp. 6. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: takacy0712@gmail.com. 7. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: inomata.orj@tmd.ac.jp. 8. Department of Biochemistry, Japan; National Cerebral and Cardiovascular Center Research Institute, Japan. Electronic address: jhino@ncvc.go.jp. 9. Department of Biochemistry, Japan; National Cerebral and Cardiovascular Center Research Institute, Japan. Electronic address: miyazato@ncvc.go.jp. 10. Department of Regenerative Medicine and Tissue Engineering, Japan; National Cerebral and Cardiovascular Center Research Institute, Japan. Electronic address: hosoda.hiroshi.ri@ncvc.go.jp. 11. National Cerebral and Cardiovascular Center Research Institute, Japan. Electronic address: kangawa_k@ncvc.go.jp. 12. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: ynakagawa.orj@tmd.ac.jp. 13. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: katagiri.orj@tmd.ac.jp. 14. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: miyatake.orj@tmd.ac.jp. 15. Center for Stem Cells and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: sekiya.arm@tmd.ac.jp. 16. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: munetaorj3255@gmail.com. 17. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: koga.orj@tmd.ac.jp.
Abstract
OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.
OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.
Authors: Leia C Shuhaibar; Nabil Kaci; Jeremy R Egbert; Thibault Horville; Léa Loisay; Giulia Vigone; Tracy F Uliasz; Emilie Dambroise; Mark R Swingle; Richard E Honkanen; Martin Biosse Duplan; Laurinda A Jaffe; Laurence Legeai-Mallet Journal: JCI Insight Date: 2021-05-10