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Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint
BACKGROUND: Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Inflammation of the infrapatellar fat pad (IFP) and synovial membrane (IFP surface) plays essential roles in persistent pain development...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320593/ https://www.ncbi.nlm.nih.gov/pubmed/30611247 http://dx.doi.org/10.1186/s12891-018-2391-1 |
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author | Inomata, Kei Tsuji, Kunikazu Onuma, Hiroaki Hoshino, Takashi Udo, Mio Akiyama, Masako Nakagawa, Yusuke Katagiri, Hiroki Miyatake, Kazumasa Sekiya, Ichiro Muneta, Takeshi Koga, Hideyuki |
author_facet | Inomata, Kei Tsuji, Kunikazu Onuma, Hiroaki Hoshino, Takashi Udo, Mio Akiyama, Masako Nakagawa, Yusuke Katagiri, Hiroki Miyatake, Kazumasa Sekiya, Ichiro Muneta, Takeshi Koga, Hideyuki |
author_sort | Inomata, Kei |
collection | PubMed |
description | BACKGROUND: Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Inflammation of the infrapatellar fat pad (IFP) and synovial membrane (IFP surface) plays essential roles in persistent pain development in patients with OA. To identify the point during the inflammatory process critical for persistent pain development, we performed a time course histological analysis in a rat arthritis model. METHODS: Wistar rats received single intra-articular injection of monoiodoacetic acid (MIA, 0.2 or 1.0 mg/30 μL) in the right knees or phosphate-buffered saline (PBS, 30 μL) as a control in the left knees. Pain avoidance behaviors (weight-bearing asymmetry and tactile hypersensitivity of the plantar surface of the hind paw) were evaluated on days 0, 1, 3, 5, 7, and 14 after injection. Histological assessments of the knee joint were performed on days 0, 1, 3, 5, and 7 after MIA injection. RESULTS: Weight-bearing asymmetry was observed along with the onset of acute inflammation in both the low- (0.2 mg) and high-dose (1.0 mg) groups. In the low-dose group, weight-bearing asymmetry was completely reversed on day 10, indicating that joint pain seemed to alleviate between days 7 and 10. In contrast, we observed persistent joint pain after day 10 in the high-dose group. Histological assessments of the high-dose group indicated that the initial sign of inflammatory responses was observed in the perivascular region inside the IFP. Inflammatory cell infiltration from the perivascular region to the parenchymal region of the IFP was observed on day 3 and reached the IFP surface (synovial membrane) on day 7. Extensive fibrosis throughout the IFP was observed between days 5 and 7 after MIA injection. CONCLUSION: Our data indicated that acute joint pain occurs along with the onset of acute inflammatory process. Irreversible structural changes in the IFP, such as extensive fibrosis, are observed prior to persistent pain development. Thus, we consider that this process may play important roles in persistent pain development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12891-018-2391-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6320593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63205932019-01-08 Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint Inomata, Kei Tsuji, Kunikazu Onuma, Hiroaki Hoshino, Takashi Udo, Mio Akiyama, Masako Nakagawa, Yusuke Katagiri, Hiroki Miyatake, Kazumasa Sekiya, Ichiro Muneta, Takeshi Koga, Hideyuki BMC Musculoskelet Disord Research Article BACKGROUND: Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Inflammation of the infrapatellar fat pad (IFP) and synovial membrane (IFP surface) plays essential roles in persistent pain development in patients with OA. To identify the point during the inflammatory process critical for persistent pain development, we performed a time course histological analysis in a rat arthritis model. METHODS: Wistar rats received single intra-articular injection of monoiodoacetic acid (MIA, 0.2 or 1.0 mg/30 μL) in the right knees or phosphate-buffered saline (PBS, 30 μL) as a control in the left knees. Pain avoidance behaviors (weight-bearing asymmetry and tactile hypersensitivity of the plantar surface of the hind paw) were evaluated on days 0, 1, 3, 5, 7, and 14 after injection. Histological assessments of the knee joint were performed on days 0, 1, 3, 5, and 7 after MIA injection. RESULTS: Weight-bearing asymmetry was observed along with the onset of acute inflammation in both the low- (0.2 mg) and high-dose (1.0 mg) groups. In the low-dose group, weight-bearing asymmetry was completely reversed on day 10, indicating that joint pain seemed to alleviate between days 7 and 10. In contrast, we observed persistent joint pain after day 10 in the high-dose group. Histological assessments of the high-dose group indicated that the initial sign of inflammatory responses was observed in the perivascular region inside the IFP. Inflammatory cell infiltration from the perivascular region to the parenchymal region of the IFP was observed on day 3 and reached the IFP surface (synovial membrane) on day 7. Extensive fibrosis throughout the IFP was observed between days 5 and 7 after MIA injection. CONCLUSION: Our data indicated that acute joint pain occurs along with the onset of acute inflammatory process. Irreversible structural changes in the IFP, such as extensive fibrosis, are observed prior to persistent pain development. Thus, we consider that this process may play important roles in persistent pain development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12891-018-2391-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-05 /pmc/articles/PMC6320593/ /pubmed/30611247 http://dx.doi.org/10.1186/s12891-018-2391-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Inomata, Kei Tsuji, Kunikazu Onuma, Hiroaki Hoshino, Takashi Udo, Mio Akiyama, Masako Nakagawa, Yusuke Katagiri, Hiroki Miyatake, Kazumasa Sekiya, Ichiro Muneta, Takeshi Koga, Hideyuki Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title | Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title_full | Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title_fullStr | Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title_full_unstemmed | Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title_short | Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
title_sort | time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320593/ https://www.ncbi.nlm.nih.gov/pubmed/30611247 http://dx.doi.org/10.1186/s12891-018-2391-1 |
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