Name: 著者スポットライト:Tuinaによる変形性膝関節症の治療-新しい視点
Uploaded: 2024-01-12T13:15:00
Description: Watch this Scientific Journal Video about Treating Knee Osteoarthritis with Tuina - A New Perspective at JoVE.com

この研究は、中国国家自然科学基金会(NO.82105042、82205302)の支援を受けています。上海ポスドク優秀プログラム(NO.2020371);中国ポスドク科学基金会(NO.2021M692156);上海セーリングプログラム(NO.20YF1450900);中国伝統医学と西洋医学を統合した岳陽病院の科学財団(NO.2021yygq03)。資金提供者は、研究のデザイン、実施、執筆に関与していなかった。

すべての実験は、世界医師会ヘルシンキ宣言の規定に準拠した上海中医薬大学動物管理委員会(承認番号:SYXK2018-0040)によって承認および監督されました。
1.動物の調製
<ol><li>ハウス32 Sprague Dawley(SD)オスラット、8週齢、体重180〜220g、特定の病原体のない飼育装置で、24±〜2°C、湿度60%、24〜2°C、湿度60%で12時間の明サイクル、標準的なげっ歯類のペレット食。?...

変形性膝関節症に対するTuinaマッサージの治療可能性

<ol>
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G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+of+knee+osteoarthritis+features+on+magnetic+resonance+imaging+in+asymptomatic+uninjured+adults:+a+systematic+review+and+meta-analysis.">Prevalence of knee osteoarthritis features on magnetic resonance imaging in asymptomatic uninjured adults: a systematic review and meta-analysis.</a> Br J Sports Med. 53 (20), 1268-1278 (2019).</li><li>Safiri, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=regional+and+national+burden+of+osteoarthritis+1990-2017:+a+systematic+analysis+of+the+Global+Burden+of+Disease+Study+2017.">regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.</a> Ann Rheum Dis. 79 (6), 819-828 (2020).</li><li>Kong, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traditional+Chinese+exercises+on+pain+and+disability+in+middle-aged+and+elderly+patients+with+neck+pain:+a+systematic+review+and+meta-analysis+of+randomized+controlled+trials.">Traditional Chinese exercises on pain and disability in middle-aged and elderly patients with neck pain: a systematic review and meta-analysis of randomized controlled trials.</a> Front Aging Neurosci. 14, 912-945 (2022).</li><li>Nevitt, M. 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J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interpretation+and+evaluation+of+the+Chinese+Osteoarthritis+Treatment+Guidelines+(2021+Edition).">Interpretation and evaluation of the Chinese Osteoarthritis Treatment Guidelines (2021 Edition).</a> Chinese Journal of Evidence-Based Medicine. 22 (06), 621-627 (2022).</li><li>Chen, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+an+epidemiological+survey+on+the+prevalence+of+osteoarthritis+of+the+knee+in+a+middle-aged+and+elderly+population+in+China.">Design of an epidemiological survey on the prevalence of osteoarthritis of the knee in a middle-aged and elderly population in China.</a> Journal of Hebei Medical University. 36 (04), 487-490 (2015).</li><li>Shao, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Study+on+the+mechanism+of+regulating+the+&amp;#34;balance+of+tendon+and+bone+force&amp;#34;+in+the+treatment+of+knee+osteoarthritis+by+Tui+Na+manipulation.">Study on the mechanism of regulating the &amp;#34;balance of tendon and bone force&amp;#34; in the treatment of knee osteoarthritis by Tui Na manipulation.</a> Shanghai University of Traditional Chinese Medicine. , 107-108 (2020).</li><li>Liu, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+and+mechanism+of+PD-1/PD-L1+pathway+in+osteoarthritis+in+mice.">Role and mechanism of PD-1/PD-L1 pathway in osteoarthritis in mice.</a> Shandong University. , 130-134 (2020).</li><li>Shoujian, <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PD-1+promotes+the+repair+and+regeneration+of+contused+skeletal+muscle+by+regulating+Treg+cells+and+macrophages.">PD-1 promotes the repair and regeneration of contused skeletal muscle by regulating Treg cells and macrophages.</a> Shanghai Institute of Physical Education. , 54-58 (2020).</li><li>Levinger, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+level+of+FoxO1+and+IL-15+in+skeletal+muscle,+serum+and+synovial+fluid+in+people+with+knee+osteoarthritis:+a+case+control+study.">The level of FoxO1 and IL-15 in skeletal muscle, serum and synovial fluid in people with knee osteoarthritis: a case control study.</a> Osteoporos Int. 27 (6), 2137-2143 (2016).</li><li>Niu, Q., Xie, C., Jiang, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+Chinese+medicine+based+on+PI3K/AKT+signaling+pathway+for+the+treatment+of+knee+osteoarthritis.">Advances in Chinese medicine based on PI3K/AKT signaling pathway for the treatment of knee osteoarthritis.</a> Massage and Rehabilitation Medicine. , 1-5 (2022).</li><li>Liu, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blocking+of+checkpoint+receptor+PD-L1+aggravates+osteoarthritis+in+macrophage-dependent+manner+in+the+mice+model.">Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model.</a> Int J Immunopathol Pharmacol. 33, 2058-2073 (2019).</li><li>Molanouri, S. 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C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Massage+therapy+has+short-term+benefits+for+people+with+common+musculoskeletal+disorders+compared+to+no+treatment:+a+systematic+review.">Massage therapy has short-term benefits for people with common musculoskeletal disorders compared to no treatment: a systematic review.</a> J Physiother. 61 (3), 106-116 (2015).</li><li>Xu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effectiveness+of+tui+na+in+treating+pain+after+total+knee+replacement+for+knee+osteoarthritis.">Effectiveness of tui na in treating pain after total knee replacement for knee osteoarthritis.</a> Chinese Tissue Engineering Research. 25 (18), 2840-2845 (2021).</li><li>Ali, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Massage+therapy+and+quality+of+life+in+osteoarthritis+of+the+knee:+a+qualitative+study.">Massage therapy and quality of life in osteoarthritis of the knee: a qualitative study.</a> Pain Med. 18 (6), 1168-1175 (2017).</li><li>Yoh, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intra-articular+injection+of+monoiodoacetate+induces+diverse+hip+osteoarthritis+in+rats,+depending+on+its+dose.">Intra-articular injection of monoiodoacetate induces diverse hip osteoarthritis in rats, depending on its dose.</a> BMC Musculoskelet Disord. 23 (1), 494-487 (2022).</li><li>Lockwood, S. 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本研究は、標準化された行動指標を用いて、推拿介入後のKOAの改善を評価し、KOAに対するTuinaのメカニズムと骨格筋とKOAとの関連を調査することを目的としています。薬物療法や外科的治療とは異なり、推拿は運動系、免疫系、内分泌系にプラスの調節効果をもたらします。推拿は、さまざまな標的に作用することにより、病気によって引き起こされる炎症や痛みを和らげることができます?...

変形性膝関節症(KOA)は、慢性的な痛みと障害を特徴とする一般的な変性変形性関節症であり、比較的重度のKOAは関節に不可逆的な構造的損傷をもたらします1。KOAの世界的な有病率の高さは、世界的な公衆衛生上の大きな課題となっており2,3、患者の生活の質を著しく損なう4,5。研究によると、KOAは世界中で2億6,000万人以上が罹患しています6。人口の高齢化に伴い、中国におけるKOAの総有病率は40歳以上で17.0%と高く、罹患者の家族に大きな負担をかけています7,8。
中国医学では、KOAは「麻痺」の範疇に属し9、黄帝の内科古典は腱、骨、肉を麻痺と関連付けています。したがって、KOAでは、軟骨、筋肉、滑膜、および膝関節周辺の他の組織間の接続に注意を払う必要があります。現代医学では、関節炎の免疫恒常性の主要な構成要素である筋肉と骨の両方の炎症がKOAの痛みの進行を促進します。しかし、ほとんどの研究は骨関節の軟骨炎症と滑膜炎症に焦点を当てており、骨格筋の炎症現象を調べた論文は不足しています。したがって、炎症における骨格筋の役割に関するさらなる研究は、KOAをより包括的に理解し、より効果的な治療法のアイデアを提供するために必要です。文献のレビューでは、免疫関連因子プログラム死リガンド1(PD-L1)の阻害がKOA10,11の進行を悪化させ、KOA12患者の骨格筋におけるIL-15およびFOXO1の発現の違い、および末期KOA患者の有意な骨格筋の炎症があることを発見しました。 これは歩行の変化にも関連していました。骨格筋はIL-6などの炎症性免疫に密接に関連する因子も分泌することがあり、TNF-αはPD-L1経路やKOAにも密接に関連していることが示されています13,14,15。
現在、KOAの利用可能な治療法には、体重管理、運動、投薬、および手術が含まれ、通常は関節内注射、鎮痛薬、関節鏡視下手術、および膝の人工骨切り術が含まれます16。現在、KOA疾患の進行を完全に止めたり元に戻したりすることはできず、KOAの痛みの根底にある複雑なメカニズムを明確に理解していないと、KOA患者は鎮痛薬の過剰使用や副作用の発生率が高くなるリスクがあります8。ほとんどの治療戦略は短期間しか効果がなく、病気の病因ではなく、症状の一時的な緩和にのみ焦点を当てています。したがって、KOAの痛みは依然として治療の優先事項であり、課題であり、深刻な臨床的課題を提起しています。しかし、推拿はKOA治療において患部の関節周辺の骨格筋を直接刺激することができ、いくつかの利点をもたらすことができます。前の説明と組み合わせると、KOAにおける骨格筋組織の役割を研究するための理想的な治療法であり、炎症における骨格筋組織の役割を明らかにすることは、KOAのTuinaにより良い理論的サポートを提供することもできます。
研究によると、マッサージ療法、オステオパシー手技療法、脊椎マニピュレーションは、痛みを和らげ、身体機能を回復させるのに役立つことが示されています17,18。これらの操作は、局所的な炎症に作用し、外部の機械的作用によって痙攣や鎮痛を和らげることができます。人工膝関節全置換術後の痛みを和らげ、鎮痛薬の使用を減らし、術後の回復を促進し、生体力学的バランスを改善することができます19。スウェーデン式マッサージは変形性関節症の治療に有効であり、ストレスを軽減し、生活の質を向上させることができます20。KOAに対する推拿の治療効果は、特定の研究によって先行されています。.
本実験では、ラットにおけるMIA誘導KOAモデルを用いて、骨格筋におけるPD-L1および関連する炎症因子の発現がKOAを誘導し、その発生を促進することができるかどうかを検討します。また、炎症因子の発現増加によって引き起こされるKOAの症状を緩和できるかどうかを調べるために、Tuinaも実施されます。推拿はPD-L1阻害と組み合わされ、KOAの発症と痛みに影響を与える骨格筋の炎症における推拿を介したPD-1経路との関連を実証し、KOAにおける推拿介入の治療メカニズムに関するさらなるマルチレベル研究の基礎を築きます。
要約すると、本論文は、KOAの発症における骨格筋の炎症とその痛みのメカニズムの調査と精緻化、およびKOAに対するトゥイナの治療効果について、免疫炎症因子の発現の観点から説明し、行動関連の指標と組み合わせて、伝統的な中国医学における「腱と骨の不均衡」理論の現代的な研究証拠を提供します。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Anti-PD-L1</td>
			<td>Abcam, Cambridge, MA, USA</td>
			<td>ab80276</td>
			<td></td>
		</tr>
		<tr>
			<td>electric von Frey esthesiometer&#160;</td>
			<td>IITC/Life Science, Woodland Hills, CA, USA</td>
			<td>ALMEMO 2450</td>
			<td></td>
		</tr>
		<tr>
			<td>GraphPad Prism 9.0</td>
			<td>GraphPad Software</td>
			<td></td>
			<td>Software for stastistical analysis</td>
		</tr>
		<tr>
			<td>monosodium iodoacetate</td>
			<td>Sigma-Aldrich Inc</td>
			<td>I9148</td>
			<td>Resolved into normal saline for injection</td>
		</tr>
		<tr>
			<td>pentasorbital sodium</td>
			<td>Sigma-Aldrich Inc</td>
			<td>P3761</td>
			<td></td>
		</tr>
		<tr>
			<td>Sprague Dawley (SD) male rats</td>
			<td>Shanghai Jihui Experimental Animal Breeding Co., Ltd</td>
			<td>No. SCXK (Hu) 2017-0012</td>
			<td></td>
		</tr>
		<tr>
			<td>thermal analgesia tester</td>
			<td>IITC/Life Science</td>
			<td>Model 390</td>
			<td></td>
		</tr>
	</tbody>
</table>

tuina intervention in sodium monoiodoacetate injection-induced rat model of knee osteoarthritis

一般的な変性関節症である変形性膝関節症(KOA)は、慢性的な痛みと障害を特徴とし、関節の修復不可能な構造的損傷に進行する可能性があります。KOAにおける関節軟骨、筋肉、滑膜、および膝関節を取り巻くその他の組織間の関連性の調査は非常に重要です。現在、KOAの管理には、ライフスタイルの変更、運動、投薬、および外科的介入が含まれます。しかし、KOA関連疼痛の複雑なメカニズムの解明はまだ進んでいません。その結果、KOA疼痛は依然として重要な臨床的課題であり、治療上の優先事項である。推拿は、運動系、免疫系、内分泌系に調節効果があることがわかっており、 炎症因子のアップレギュレーションによって引き起こされるKOA症状を緩和するかどうか、さらに、骨格筋の炎症因子がKOAの進行を増強できるかどうか。
32匹の雄のSprague Dawley(SD)ラット(180-220 g)を、抗PD-L1+Tuina(グループA)、モデル(グループB)、Tuina(グループC)、および偽手術(グループD)の8匹ずつの4つのグループに無作為に割り付けました。A群、B群、C群では、25μLのモノヨード酢酸ナトリウム(MIA)溶液(4mgのMIAを25μLの滅菌生理食塩水で希釈したもの)を右膝関節腔に注入し、D群に対しては同量の滅菌生理食塩水を注入した。すべてのグループは、注射前および注射後2、9、および16日後に、最もストレスの少ないテスト(足の機械的離脱閾値、足の離脱熱潜伏、右膝関節の腫れ、Lequesne MGスコア、皮膚温度)を使用して評価されました。

Knee osteoarthritis (KOA) is a common degenerative osteoarthritis, characterized by chronic pain and disability, and relatively severe KOA will lead to irreversible structural damage to the joint1. The high global prevalence of KOA has become a major global public health challenge2,3, which seriously impairs the quality of life of patients4,5. Studies have shown that KOA affects more than 260 million people worldwide6. With the aging of the population, the total prevalence rate of KOA in China is as high as 17.0% over the age of 40, which puts a heavy burden on the families of those affected7,8.
According to Chinese medicine, KOA belongs to the category of &#34;paralysis&#34;9, and the Yellow Emperor&#39;s Classic of Internal Medicine associates tendons, bones, and flesh with paralysis. Hence, we need to pay attention to the connection between the cartilage, muscle, synovium, as well as other tissues around the knee joint in KOA. In modern medicine, both muscle and bone inflammation, which are major components of the immune homeostasis of arthritis, drive the progression of KOA pain. However, most studies focus on cartilage inflammation and synovial inflammation in bone joints, and there is a paucity of articles examining inflammatory phenomena in skeletal muscles. Therefore, more research on the role of skeletal muscle in inflammation is needed to gain a more comprehensive understanding of KOA and provide ideas for more effective treatment modalities. In a review of the literature, we found that inhibition of the immune-related factor programmed death ligand 1 (PD-L1) exacerbated the progression of KOA10,11 and that there was differential expression of IL-15 and FOXO1 in the skeletal muscle of patients with KOA12, as well as significant skeletal muscle inflammation in patients with end-stage KOA, which was also associated with changes in gait. It has been shown that the skeletal muscle can also secrete factors closely related to inflammatory immunity such as IL-6, and that TNF-&#945; is also closely related to the PD-L1 pathway and KOA13,14,15.
Currently, available treatments for KOA include weight control, exercise, medication, and surgery, which usually include intra-articular injections, analgesic medication, arthroscopic surgery, and periprosthetic osteotomy of the knee16. Currently, KOA disease progression cannot be completely stopped or reversed, and without a clear understanding of the complex mechanisms underlying KOA pain, KOA patients are at risk for overuse of analgesic medications and a high incidence of side effects8. Most treatment strategies are effective only for short periods and focus only on the temporary relief of symptoms rather than on the pathogenesis of the disease. Therefore, KOA pain remains a priority and a challenge for treatment, posing a serious clinical challenge. However, Tuina can directly stimulate the skeletal muscles around the affected joint in KOA treatment and can provide some benefits. Combined with the previous description, it is the ideal therapy to study the role of skeletal muscle tissue in KOA, and clarifying the role of skeletal muscle tissue in inflammation can also provide better theoretical support for Tuina of KOA.
Studies have shown that massage therapy, osteopathic manipulative therapy, and spinal manipulation can help relieve pain and restore body function17,18. These manipulations can act on local inflammation and relieve spasms and analgesia through external mechanical action. They can relieve pain after total knee arthroplasty, reduce the use of analgesic drugs, promote postoperative recovery, and improve biomechanical balance19. Swedish massage is feasible in the treatment of osteoarthritis and can reduce stress and improve quality of life20. The therapeutic effect of Tuina on KOA has been preceded by certain studies.
In this experiment, our team will explore whether the expression of PD-L1 and related inflammatory factors in skeletal muscle can induce KOA and promote its development based on the MIA-induced KOA model in rats. Tuina will also be implemented to see whether it can alleviate KOA symptoms caused by increased inflammatory factor expression. Tuina will be combined with PD-L1 inhibition to demonstrate the association between Tuina-mediated PD-1 pathway in skeletal muscle inflammation affecting KOA development and pain, laying the foundation for further multi-level studies on the therapeutic mechanisms of Tuina intervention in KOA.
In summary, this paper describes the investigation and elaboration of the mechanisms of skeletal muscle inflammation in the development of KOA and its pain, as well as the therapeutic effects of Tuina on KOA, from the perspective of immune-inflammatory factor expression, combined with behavioral related indicators, to provide modern research evidence for the &#34;imbalance of tendon and bone&#34; theory in traditional Chinese medicine.

著者スポットライト:Tuinaによる変形性膝関節症の治療-新しい視点 

変形性膝関節症のモノヨード酢酸ナトリウム注射誘発ラットモデルにおける推拿介入

We are trying to broaden the views on the research of knee osteoarthritis by introducing the perspective of refocusing on muscle inflammation during the pathological process of the KOA. There is a recent trend in non-pharmacological therapy treating the knee osteoarthritis. Therapy measures of traditional Chinese medicine, such as TNA and acupuncture, are receiving more and more recognition.There is a calling for detailed mechanism in the treatment. Our experiments indicates the possibility of chronic muscle inflammation in the process of knee osteoarthritis. It also points out the possibility of non-pharmacological therapy such as TNA to treat and control it.

説明されているプロトコルは、中国伝統医学と西洋医学の統合の岳陽病院の臨床現場で実施されました。図1はラットに押し込まれたツボの正確な位置を示し、表1はこれらのツボを刺激することの一般的な利点を示しています。表2および表3は、PD-1経路阻害がない場合でも、推拿療法によって達成された顕著な疼痛緩和の説得力の?...

Watch this Scientific Journal Video about Treating Knee Osteoarthritis with Tuina - A New Perspective at JoVE.com

このプロトコルはKOAの動物モデルでTuinaの適用に参照を提供する膝の変形性関節症(KOA)のナトリウムのmonoiodoacetateの注入誘導されたラットモデルにおけるTuinaの介在の方法を記述する。このプロトコルは、KOAに対するTuinaの効果的なメカニズムも研究しており、その結果はその応用を促進するのに役立ちます。

Knee osteoarthritis (KOA), a common degenerative joint disorder, is characterized by chronic pain and disability, which can progress to irreparable ...

変形性膝関節症研究の視野を広げるために、KOAの病態過程における筋の炎症に再び着目するという視点を導入しています。変形性膝関節症を治療する非薬理学的治療の最近の傾向があります。TNAや鍼灸などの伝統的な中国医学の治療法は、ますます認識されています。治療には詳細なメカニズムが求められています。私たちの実験は、変形性膝関節症の過程における慢性的な筋肉の炎症の可能性を示しています。また、TNAなどの非薬物療法で治療・制御できる可能性も指摘しています。

tuina-intervention-sodium-monoiodoacetate-injection-induced-rat-model

Research

JoVE Journal

Medicine

Tuina Intervention in Sodium Monoiodoacetate Injection-Induced Rat Model of Knee Osteoarthritis

Knee osteoarthritis (KOA), a common degenerative joint disorder, is characterized by chronic pain and disability, which can progress to irreparable structural damage of the joint. Investigations into the link between articular cartilage, muscles, synovium, and other tissues surrounding the knee joint in KOA are of great importance. Currently, managing KOA includes lifestyle modifications, exercise, medication, and surgical interventions; however, the elucidation of the intricate mechanisms underlying KOA-related pain is still lacking. Consequently, KOA pain remains a key clinical challenge and a therapeutic priority. Tuina has been found to have a regulatory effect on the motor, immune, and endocrine systems, prompting the exploration of whether Tuina could alleviate KOA symptoms, caused by the upregulation of inflammatory factors, and further, if the inflammatory factors in skeletal muscle can augment the progression of KOA.
We randomized 32 male Sprague Dawley (SD) rats (180-220 g) into four groups of eight animals each: antiPD-L1+Tuina (group A), model (group B), Tuina (group C), and sham surgery (group D). For groups A, B, and C, we injected 25 &#181;L of sodium monoiodoacetate (MIA) solution (4 mg MIA diluted in 25 &#181;L of sterile saline solution) into the right knee joint cavity, and for group D, the same amount of sterile physiological saline was injected. All the groups were evaluated using the least to most stressful tests (paw mechanical withdrawal threshold, paw withdrawal thermal latency, swelling of the right knee joint, Lequesne MG score, skin temperature) before injection and 2, 9, and 16 days after injection.

This protocol describes the methods of Tuina intervention in sodium monoiodoacetate injection-induced rat model of knee osteoarthritis (KOA), which provides a reference for the application of Tuina in KOA animal models. This protocol also studies the effective mechanism of Tuina for KOA, and the results will help promote its application.