This study is supported by National Natural Science Foundation of China (NO.82105042, 82205302); Shanghai Post-doctoral Excellence Program (NO.2020371); China Postdoctoral Science Foundation (NO.2021M692156); Shanghai Sailing Program (NO.20YF1450900); Science Foundation of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (NO.2021yygq03). The funders had no role in the design, execution, or writing of the study.

All experiments were approved and supervised by the Animal Care and Use Committee of the Shanghai University of Traditional Chinese Medicine (approval number: SYXK2018-0040), which conforms to the stipulations in the World Medical Association Helsinki Declaration.
1. Animal preparation
<ol>
	<li>House 32 Sprague Dawley (SD) male rats aged 8 weeks and weighing 180-220 g in a specific pathogen-free housing apparatus under 12 h light/12 h dark cycles at 24 &#177; 2 &#176;C and 60% humidity with a standard rodent pellet diet. All experimental operations on animals comply with the welfare ethics of experimental animals and animal experimental safety regulations.</li>
	<li>Randomize and cage rats into four groups of eight animals each after 1 week of adaptive feeding: antiPD-L1+Tuina (group A), model (group B), Tuina (group C), and sham surgery (group D).</li>
</ol>
2. Intra-articular injection of monosodium iodoacetate (MIA) in the knee
NOTE: Except for group D, the KOA rat model will be prepared by the knee joint cavity injection of MIA in all the groups. For group D, inject 25 &#181;L of sterile physiological saline into the right knee joint cavity.
<ol>
	<li>Anesthetize the rat by placing it in an anesthetic cage and then introducing 2.5% isoflurane until it is fully anesthetized. Confirm the animal is fully anesthetized by waiting for the point when the young rat is lying on its back, its limbs stop moving, and there is no response in toe pinch (pedal reflex), palpebral reflex, and muscle relaxation.</li>
	<li>Add pet eye ointment and eye drops to the anesthetized young rats to prevent eye dryness.</li>
	<li>Shave the right hind limb of the rats and disinfect the knee joint with three alternating rounds of iodophor and 75% ethanol.</li>
	<li>To maintain a standardized experimental condition, carefully fix the knee flexion at a precise angle of 90&#176;, ensuring that the patellar ligament is oriented upwards. Subsequently, inject 25 &#181;L of MIA solution, consisting of 4 mg of MIA diluted in 25 &#181;L of sterile saline solution into the right knee joint cavity of the rats. 
	NOTE: This injection was carried out with a specialized microinjector, ensuring accuracy and consistency in the procedure21,22,23. Put the rats back into the cages until they wake up. The animal that has undergone surgery is not returned to the company of other animals until fully recovered.</li>
	<li>At the end of the study, euthanize the rats by injecting 1% pentobarbital sodium as a 100 mg/kg dose.</li>
</ol>
3. Implementation of Tuina
NOTE: The implementation ofTuina will be guided by the theory that &#34;for patients with tendon and bone imbalance, tendons need to be treated first&#34;. Both groups A and B started the intervention on the first day after the successful evaluation of the model, and both groups were operated once a day for 14 days. The remaining two groups were only observed for 14 days without any intervention. The operators of the manipulation must be strictly trained before the experiment to ensure the consistency of force, frequency, and rhythm.
<ol>
	<li>Accurately locate the rat acupuncture point, including EX-LE4, ST35, SP10, ST34, SP9, and GB34 (Figure 1 and Table 1), where finger kneading methods will be carried out by using Experimental Acupuncture24.</li>
	<li>Fix the rat in the prone position on the rat fixation equipment.</li>
	<li>After it is quiet and the lower limbs are relaxed, knead the EX-LE4 and ST35 of the affected limb with the thumb and the index finger simultaneously for 4 min at 120-140 times/min.</li>
	<li>Knead the anterior and medial-lateral muscles of the affected limb with the thumb and the index finger for 3 min at 120-140 times/min, focusing on the SP10, ST34, and the muscles near the knee joint. Emphasize the manipulation of those stiff muscles with an intensity so that the rat does not struggle.</li>
	<li>Knead the posterior calf muscles of the affected limb from top to bottom for 3 min at 120-140 times/min by using the thumb, the index finger, and the middle finger. To fully expose the treatment area, use the ring finger and the little finger to hold the ankle joint of the affected limb and gently tug on the affected limb. Focus on SP9, GB34, and the muscles near the knee joint with emphasis on the rigid muscles and intensity so that the rat does not struggle.</li>
</ol>
4. Measurement of behavioral index
<ol>
	<li>Measurement of plantar mechanical pain threshold 
	NOTE: Measure plantar mechanical pain thresholds 1 day before MIA injection as well as 2, 9, and 16 days after injection.
	<ol>
		<li>Bring the rats to a plantar test room with a stainless-steel grid bottom and a plastic cage body in a quiet environment at room temperature (22 &#177; 2) &#176;C for 30 min of adaptation.</li>
		<li>Use an electronic mechanical pain tester with a plastic test needle of 0.8 mm in diameter to stimulate the central area of the right hindfoot of the rats vertically. Evenly and gradually increase the stimulation intensity until the rats show paw retraction and avoidance reactions.</li>
		<li>Record the reading of the electronic screen as the mechanical pain threshold of the right plantar foot of the rat.</li>
		<li>Measure each rat 5x at 5 min intervals.</li>
		<li>Remove the maximum and minimum values from the five values. Take the average value of the middle three values through the trimmed mean method as the result (Table 2).</li>
	</ol>
	</li>
	<li>Measurement of paw mechanical withdrawal threshold 
	NOTE: Measure paw mechanical withdrawal threshold 1 day before MIA injection, 2, 9, and 16 days after injection.
	<ol>
		<li>Bring the rats to a heated plantar test room with a 30 &#176;C glass bottom and a plastic cage body in a quiet environment at room temperature (22 &#177; 2) &#176;C for 30 min of adaption.</li>
		<li>Stimulate the right hind plantar center area with a light source heating device at a stimulation temperature of 65 &#176;C until the rat shows a paw retraction and avoidance response.</li>
		<li>Record the time reading of the electronic screen as the right plantar thermal pain threshold of the rat.</li>
		<li>Measure each rat 5x continuously at 5 min intervals.</li>
		<li>Remove the maximum and minimum values from the five values. Take the average value of the middle three values through the trimmed mean method as the result (Table 3).</li>
	</ol>
	</li>
</ol>
5. Measurement of swelling of the right knee joint
NOTE: Measure the swelling of the right knee joint of rats 1 day before MIA injection, 2, 9, and 16 days after the injection.
<ol>
	<li>Anesthetize the rat by placing it in an anesthetic cage and exposing it to 2.5% isoflurane until it is fully anesthetized.</li>
	<li>Place the rat in a flat position on the operating table.</li>
	<li>Measure the width of the right knee joint with vernier calipers (Figure 2 and Table 4).</li>
</ol>
6. Measurement of the Lequesne MG score
NOTE: Measure the Lequesne MG score in rats at 2, 9, and 16 days after MIA injection. Lequesne et al developed an index of severity for osteoarthritis for the hip (ISH), which can be used to assess the effectiveness of therapeutic interventions. We consider four parameters: pain stimulation, gait change, joint mobility, and joint swelling.
<ol>
	<li>Bring the rats to a manipulation platform in a quiet environment at room temperature (22 &#177; 2) &#176;C.</li>
	<li>Have two operators, blinded to each other, measure the local pain stimulation response, gait change, joint movement, and joint swelling.
	<ol>
		<li>Stimulate the lateral side of the right knee joint with a plastic test needle and score on a scale of 0-3 according to the response. 0 no response; 3 a good response; 1 contraction of the affected limb; 2 contraction and spasm of the affected limb, accompanied by mild generalized reactions, such as trembling, licking, and sucking.</li>
		<li>Place the rat on the operating table and observe the gait of its right hind limbs. Score on a scale of 0-3 according to the response. 0 no disturbance in the movement of the affected limb, normal running, and strong footwork; 3 the affected limb cannot participate in walking, touch the ground, or stomp on the ground; 1 mild trekking during running with strong stomps; 2 the affected limb participates in walking, but the disturbance in movement of the rats (trekking) is obvious.</li>
		<li>Flex and extend the right knee joint of the rat by hand and observe the joint mobility. Score on a scale of 0-3 according to the response. 0 joint mobility angle of more than 90&#176;; 3 joint mobility angle of less than 15&#176;; 1 joint mobility angle or 45&#176;-90&#176;; 2 joint mobility angle of 15&#176;-45&#176;.</li>
		<li>Touch the right knee joint of the rat and compare the response with that of a normal rat. Score on a scale of 0-2 according to the response. 0 no obvious swelling and visible bony markings; 2 marked swelling and no bony markings; 1 mild swelling and superficial bony markings.</li>
		<li>Add these scores to produce the Lequesne MG score for each rat and calculate the average value through the trimmed method (Table 5).</li>
	</ol>
	</li>
</ol>
7. Measurement of skin temperature
NOTE: Measure the skin temperature 1 day before MIA injection and 9 and 16 days after injection.
<ol>
	<li>Anesthetize the rat by placing it in an anesthetic cage and then introducing isoflurane until it is fully anesthetized.</li>
	<li>Place the rat in a lateral position on the operating table, at room temperature (22 &#177; 2) &#176;C.</li>
	<li>Straighten the right knee joint by gently grasping the foot with the hand. Photograph to determine the skin temperature by using a Filr infrared camera.</li>
	<li>Read the skin temperature of the knee joint and around the knee joint of the rat by using supporting editing software. Set control points at the ankle joint and knee joint where the temperature gradually decreases.</li>
</ol>
8. Statistical analysis
<ol>
	<li>Use statistical software to express the experimental data in quartiles.</li>
	<li>Use the trim mean method to deal with the outliers. The outcomes of behavioral tests are noted as the mean &#177; standard error of the mean.</li>
	<li>Perform independent samples t-test for comparison between groups. Analyze the behavioral data using a two-way repeated measure analysis of variance (ANOVA), followed by Bonferroni&#39;s multiple comparison tests. Where data do not exhibit normality or homoscedasticity, perform a non-parametric test (Kruskal-Wallis k samples). 
	NOTE: P &#60; 0.05 indicates that the differences are statistically significant. All the data meet the assumptions of the statistical tests that are applied.</li>
</ol>

Therapeutic Potential of Tuina Massage for Knee Osteoarthritis

<ol>
	<li>Katz, J. N., 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=Diagnosis+and+treatment+of+hip+and+knee+osteoarthritis:+A+review.">Diagnosis and treatment of hip and knee osteoarthritis: A review.</a> JAMA. 325 (6), 568-578 (2021).</li><li>Culvenor, A. 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. 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=Symptoms+of+knee+instability+as+risk+factors+for+recurrent+falls.">Symptoms of knee instability as risk factors for recurrent falls.</a> Arthritis Care Res (Hoboken). 68 (8), 1089-1097 (2016).</li><li>Hunter, D. J., March, L., Chew, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Osteoarthritis+in+2020+and+beyond:+a+Lancet+Commission).">Osteoarthritis in 2020 and beyond: a Lancet Commission).</a> Lancet. 396 (10264), 1711-1712 (2020).</li><li>Fan, Z. 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. M., 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=Combined+effect+of+aerobic+interval+training+and+selenium+nanoparticles+on+expression+of+IL-15+and+IL-10/TNF-alpha+ratio+in+skeletal+muscle+of+4T1+breast+cancer+mice+with+cachexia.">Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-alpha ratio in skeletal muscle of 4T1 breast cancer mice with cachexia.</a> Cytokine. 90, 100-108 (2017).</li><li>Mahmoudian, 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=Early-stage+symptomatic+osteoarthritis+of+the+knee+-+time+for+action.">Early-stage symptomatic osteoarthritis of the knee - time for action.</a> Nat Rev Rheumatol. 17 (10), 621-632 (2021).</li><li>Nahin, R. 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=Evidence-based+evaluation+of+complementary+health+approaches+for+pain+management+in+the+United+States.">Evidence-based evaluation of complementary health approaches for pain management in the United States.</a> Mayo Clin Proc. 91 (9), 1292-1306 (2016).</li><li>Bervoets, D. 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. M., 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=Characterisation+of+peripheral+and+central+components+of+the+rat+monoiodoacetate+model+of+osteoarthritis.">Characterisation of peripheral and central components of the rat monoiodoacetate model of osteoarthritis.</a> Osteoarthritis Cartilage. 27 (4), 712-722 (2019).</li><li>McCoy, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+osteoarthritis:+Comparisons+and+key+considerations.">Animal models of osteoarthritis: Comparisons and key considerations.</a> Vet Pathol. 52 (5), 803-818 (2015).</li><li>Guo, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploring+the+effect+of+pushing+on+cartilage+in+rats+with+knee+osteoarthritis+based+on+ROCK/LIMK1/Cofilin+signaling+pathway.">Exploring the effect of pushing on cartilage in rats with knee osteoarthritis based on ROCK/LIMK1/Cofilin signaling pathway.</a> Chongqing Medical University. , 42-44 (2022).</li><li>Liu, Z. F., 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=Tuina+for+peripherally-induced+neuropathic+pain:+A+review+of+analgesic+mechanism.">Tuina for peripherally-induced neuropathic pain: A review of analgesic mechanism.</a> Front Neurosci. 16, 1096-1104 (2022).</li><li>Gebremariam, 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=Subacromial+impingement+syndrome--effectiveness+of+physiotherapy+and+manual+therapy.">Subacromial impingement syndrome--effectiveness of physiotherapy and manual therapy.</a> Br J Sports Med. 48 (16), 1202-1208 (2014).</li><li>Yao, 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=Transcriptome+profiling+of+microRNAs+reveals+potential+mechanisms+of+manual+therapy+alleviating+neuropathic+pain+through+microRNA-547-3p-mediated+Map4k4/NF-kappab+signaling+pathway.">Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-kappab signaling pathway.</a> J Neuroinflammation. 19 (1), 211-221 (2022).</li><li>Valera-Calero, 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=Endocrine+response+after+cervical+manipulation+and+mobilization+in+people+with+chronic+mechanical+neck+pain:+a+randomized+controlled+trial.">Endocrine response after cervical manipulation and mobilization in people with chronic mechanical neck pain: a randomized controlled trial.</a> Eur J Phys Rehabil Med. 55 (6), 792-805 (2019).</li><li>Kovanur, S. K., 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=Measureable+changes+in+the+neuro-endocrinal+mechanism+following+spinal+manipulation.">Measureable changes in the neuro-endocrinal mechanism following spinal manipulation.</a> Med Hypotheses. 85 (6), 819-824 (2015).</li><li>Colombi, A., Testa, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+induced+by+spinal+manipulative+therapy+on+the+immune+and+endocrine+systems.">The effects induced by spinal manipulative therapy on the immune and endocrine systems.</a> Medicina (Kaunas). 55 (8), 312-314 (2019).</li><li>Afify, A., Mark, H. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluorescence+in+situ+hybridization+assessment+of+chromosome+8+copy+number+in+stage+I+and+stage+II+infiltrating+ductal+carcinoma+of+the+breast.">Fluorescence in situ hybridization assessment of chromosome 8 copy number in stage I and stage II infiltrating ductal carcinoma of the breast.</a> Cancer Genet Cytogenet. 97 (2), 101-105 (1997).</li><li>Kirby, B. 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=Mechanical+influences+on+skeletal+muscle+vascular+tone+in+humans:+insight+into+contraction-induced+rapid+vasodilatation.">Mechanical influences on skeletal muscle vascular tone in humans: insight into contraction-induced rapid vasodilatation.</a> J Physiol. 583, 861-874 (2007).</li><li>Sefton, J. M., 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=Therapeutic+massage+of+the+neck+and+shoulders+produces+changes+in+peripheral+blood+flow+when+assessed+with+dynamic+infrared+thermography.">Therapeutic massage of the neck and shoulders produces changes in peripheral blood flow when assessed with dynamic infrared thermography.</a> J Altern Complement Med. 16 (7), 723-732 (2010).</li><li>Chen, B., 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=Aerobic+exercise+combined+with+glucosamine+hydrochloride+capsules+inhibited+the+apoptosis+of+chondrocytes+in+rabbit+knee+osteoarthritis+by+affecting+TRPV5+expression.">Aerobic exercise combined with glucosamine hydrochloride capsules inhibited the apoptosis of chondrocytes in rabbit knee osteoarthritis by affecting TRPV5 expression.</a> Gene. 830, 146465 (2022).</li><li>Fang, 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=The+mechanism+of+aerobic+exercise+combined+with+glucosamine+therapy+and+circUNK+in+improving+knee+osteoarthritis+in+rabbits.">The mechanism of aerobic exercise combined with glucosamine therapy and circUNK in improving knee osteoarthritis in rabbits.</a> Life Sci. 275, 119375 (2021).</li><li>Li, X., 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=Casticin+suppresses+monoiodoacetic+acid-induced+knee+osteoarthritis+through+inhibiting+HIF-1alpha/NLRP3+inflammasome+signaling.">Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1alpha/NLRP3 inflammasome signaling.</a> Int Immunopharmacol. 86, 106745 (2020).</li><li>Ma, Z., 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=Vanillic+acid+reduces+pain-related+behavior+in+knee+osteoarthritis+rats+Through+the+inhibition+of+NLRP3+inflammasome-related+synovitis.">Vanillic acid reduces pain-related behavior in knee osteoarthritis rats Through the inhibition of NLRP3 inflammasome-related synovitis.</a> Front Pharmacol. 11, 599022 (2020).</li><li>Zhang, 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=Electroacupuncture+ameliorates+knee+osteoarthritis+in+rats+via+inhibiting+NLRP3+inflammasome+and+reducing+pyroptosis.">Electroacupuncture ameliorates knee osteoarthritis in rats via inhibiting NLRP3 inflammasome and reducing pyroptosis.</a> Mol Pain. 19, 17448069221147792 (2023).</li></ol>

The authors declare that there are no conflicts of interest.

This study aims to assess the improvement of KOA after Tuina intervention by using standardized behavioral indicators and investigate the mechanisms of Tuina for KOA and the association between skeletal muscle and KOA. Unlike pharmacological and surgical therapies, Tuina has a positive regulatory effect on the motor, immune, and endocrine systems. Tuina can relieve inflammation and pain produced by disease by acting on different targets. For example, by regulating the TLR4 pathway and miRNA, it can inhibit the activation...

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.

<table><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&amp;nbsp;</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

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.

The described protocol was implemented in a clinical setting at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Figure 1 shows the exact location of the acupoints pushed in rats, and Table 1 illustrates the common benefits of stimulating these points. Table 2 and Table 3 offer compelling evidence of notable pain relief achieved through Tuina therapy, even in the absence of PD-1 pathway inhibition. The findings presen...

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Author Spotlight: Treating Knee Osteoarthritis with Tuina - A New Perspective 

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.

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 ...

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

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1.7K Views.  Shanghai University of Traditional Chinese Medicine. We proberen de kijk op het onderzoek naar knieartrose te verbreden door het perspectief te introduceren van het opnieuw focussen op spierontsteking tijdens het pathologische proces van de KOA. Er is een recente trend in niet-medicamenteuze therapie voor de behandeling van artrose van de knie. Therapiemaatregelen van de traditionele Chinese geneeskunde, zoals TNA en acupunctuur, krijgen steeds meer erkenning.Er wordt gevraagd om een gedetailleerd mechanisme in de behandeling. Onze exper...

Video: Auteur in de schijnwerpers: knieartrose behandelen met Tuina - een nieuw perspectief 

Retinal Detachment Model in Rodents by Subretinal Injection of Sodium Hyaluronate

Subretinal injection of sodium hyaluronate is a widely accepted method of inducing retinal detachment (RD). However, the height and duration of RD or the occurrence of subretinal hemorrhage can affect photoreceptor cell death in the detached retina. Hence, it is advantageous to create reproducible RDs without subretinal hemorrhage for evaluating photoreceptor cell death. We modified a previously reported method to create bullous and persistent RDs in a reproducible location with rare occurrence of subretinal hemorrhage. The critical step of this modified method is the creation of a self-sealing scleral incision, which can prevent leakage of sodium hyaluronate after injection into the subretinal space. To make the self-sealing scleral incision, a scleral tunnel is created, followed by scleral penetration into the choroid with a 30 G needle. Although choroidal hemorrhage may occur during this step, astriction with a surgical spear reduces the rate of choroidal hemorrhage. This method allows a more reproducible and reliable model of photoreceptor death in diseases that involve RD such as rhegmatogenous RD, retinopathy of prematurity, diabetic retinopathy, central serous chorioretinopathy, and age-related macular degeneration (AMD).

Creating experimental retinal detachments with a reproducible and sustained height of detachment, and without subretinal hemorrhage, is important for studying the pathophysiology of photoreceptor cell loss in retinal disease and evaluating potential therapeutic interventions. Here, we report such a method in detail.

Subretinal injection of sodium hyaluronate is a widely accepted method of inducing retinal detachment (RD). However, the height and duration of RD or the ...

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain.
The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

Osteoarthritis (OA), or degenerative joint disease, is a debilitating condition associated with pain that remains only partially controlled by available analgesics. Animal models are being developed to improve our understanding of OA-related pain mechanisms. Here we describe the methodology for the monoiodoacetate model of OA pain in the mouse.

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The ...

Preparation, Procedures and Evaluation of Platelet-Rich Plasma Injection in the Treatment of Knee Osteoarthritis

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department. Existing non-surgical treatments have a limited effect on the repair of cartilage and on bone regeneration. Platelet-rich plasma (PRP) is an autologous bioactive substance that can repair cartilage injury and accelerate bone regeneration effectively. However, reporting of PRP preparation protocols in clinical studies is highly inconsistent, with the majority of studies providing insufficient information to allow the protocol to be reproduced. We describe a repeatable method of preparing PRP visually, the treatment of KOA using PRP intra-articular injection, and methods of evaluating the outcome. PRP was prepared using manual double centrifugation. The PRP layer was extracted from peripheral blood and used for knee joint cavity injection. Evaluations included assessments of blood platelet concentrations and clinical outcomes. Preparation of PRP by manual centrifugation requires less apparatus and is less costly than plasma filtration or centrifugation using equipment. The centrifugation time of our double centrifugation method was 6 and 5 minutes for the respective centrifugations at forces of 800 and 1400 x g, respectively, to allow for the consistent preparation of standardized PRP. However, a manual method is susceptible to operator error, and PRP batch preparation is not available. Intra-articular injection of PRP proved to be an effective treatment for knee osteoarthritis. The entire treatment procedure took less than 30 minutes, the blood platelet concentration of PRP could be standardized, and treatment was proven to be effective when evaluated by follow-up.

Knee osteoarthritis is frequently seen in the orthopedic department. We introduce in detail the entire knee osteoarthritis treatment process with platelet-rich plasma injection, including preparation, procedures, and evaluation.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department. Existing non-surgical treatments have a limited ...

Using a Knee Arthrometer to Evaluate Tissue-specific Contributions to Knee Flexion Contracture in the Rat

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ROM is called a joint contracture and results in increased morbidity. Due to the difficulty of reversing established knee contractures, early detection is important, and hence, knowing risk factors for their development is essential. The rat represents a good model with which the effect of an intervention can be studied due to the similarity of rat knee anatomy to that of humans, the rat's ability to tolerate long durations of knee immobilization in flexion, and because mechanical data can be correlated with histologic and biochemical analysis of knee tissue.
Using an automated arthrometer, we demonstrate a validated, precise, reproducible, user-independent method of measuring the extension ROM of the rat knee joint at specific torques. This arthrometer can be used to determine the effects of interventions on knee joint ROM in the rat.

The goal of the protocol is to measure the extension range of motion of the rat knee. The effects of various diseases that increase the stiffness of the knee joint and the effectiveness of treatments can be quantified.

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ...

The Lower Body Positive Pressure Treadmill for Knee Osteoarthritis Rehabilitation

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

Here, based on a clinician&#8217;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in ...

Osteoarthritis Pain Model Induced by Intra-Articular Injection of Mono-Iodoacetate in Rats

The current animal models of osteoarthritis (OA) can be divided into spontaneous models and induced models, both of which aim to simulate the pathophysiological changes of human OA. However, as the main symptom in the late stage of OA, pain affects the patients&#39; daily life, and there are not many available models. The mono-iodoacetate (MIA)-induced model is the most widely used OA pain model, mainly used in rodents. MIA is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, which causes chondrocyte death, cartilage degeneration, osteophyte, and measurable changes in animal behavior. Besides, expression changes of matrix metalloproteinase (MMP) and pro-inflammatory cytokines (IL1 &#946; and TNF &#945;) can be detected in the MIA-induced model. Those changes are consistent with OA pathophysiological conditions in humans, indicating that MIA can induce a measurable and successful OA pain model. This study aims to describe the methodology of intra-articular injection of MIA in rats and discuss the resulting pain-related behaviors and histopathological changes.

This study describes the method of intra-articular injection of mono-iodoacetate in rats and discusses the resulting pain-related behaviors and histopathological changes, which provide references for future applications.

The current animal models of osteoarthritis (OA) can be divided into spontaneous models and induced models, both of which aim to simulate the ...

Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model

One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, primarily in the hip and knee joints, which results in significant impacts on patient mobility and quality of life. To date, there are no existing curative therapies for OA able to slow down or inhibit cartilage degeneration. Presently, there is an extensive body of ongoing research to understand OA pathology and discover novel therapeutic approaches or agents that can efficiently slow down, stop, or even reverse OA. Thus, it is crucial to have a quantitative and reproducible approach to accurately evaluate OA-associated pathological changes in the joint cartilage, synovium, and subchondral bone. Currently, OA severity and progression are primarily assessed using the Osteoarthritis Research Society International (OARSI) or Mankin scoring systems. In spite of the importance of these scoring systems, they are semiquantitative and can be influenced by user subjectivity. More importantly, they fail to accurately evaluate subtle, yet important, changes in the cartilage during the early disease states or early treatment phases. The protocol we describe here uses a computerized and semiautomated histomorphometric software system to establish a standardized, rigorous, and reproducible quantitative methodology for the evaluation of joint changes in OA. This protocol presents a powerful addition to the existing systems and allows for more efficient detection of pathological changes in the joint.

The current protocol establishes a rigorous and reproducible method for quantification of morphological joint changes that accompany osteoarthritis. Application of this protocol can be valuable in monitoring disease progression and evaluating therapeutic interventions in osteoarthritis.

One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, ...

FSN Therapy for Knee Osteoarthritis Pain Management

Fu's Subcutaneous Needling for Knee Osteoarthritis Pain

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting effects in soft tissue injuries, particularly in painful musculoskeletal conditions, by providing stimulation primarily in the subcutaneous area. Osteoarthritis (OA) is the most common joint disease in adults worldwide and is often accompanied by a painful syndrome of structural changes in the peripheral joints of the knee. However, the etiology of OA pain is not fully understood, though myofascial trigger points (MTrPs) are commonly found in the lower limb muscles (so-called "tightened muscles") of patients with knee OA. 
FSN has been used in many fields for the treatment of acute pain problems and can relieve muscle contraction from MTrPs, thereby improving the local circulation. This study recruited patients with pain from knee OA into an FSN group or a transcutaneous electrical nerve stimulation (TENS) group with three treatment sessions and a follow-up over the course of 2 weeks. The results showed that FSN was effective in treating soft tissue pain around the knee with OA. This study aimed to establish and visualize three key technical indicators during FSN therapy, including the FSN needle insertion point and layer; the frequency and duration of the swaying movement; and the manipulation of the reperfusion approach. These findings have great potential for future applications in myofascial pain treatment, especially for pain management. Following this protocol could enhance FSN skills.

Author Spotlight: Fu's Subcutaneous Needling for Knee Osteoarthritis Pain  

We present a protocol for using Fu's subcutaneous needling for knee osteoarthritis pain, which combines swaying movement and reperfusion approach techniques. This protocol has great potential for future applications in myofascial pain treatment and could enhance Fu's subcutaneous needling (FSN) manipulation skills.

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting ...

Standardized Tuina Manipulation for Knee Osteoarthritis in Rats

Tuina Manipulation to Reduce Inflammation and Cartilage Loss in Knee Osteoarthritis Rats

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-&#945; was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.

Author Spotlight: Understanding the Mechanism of Tuina Manipulation in Rats 

We present a protocol for Tuina manipulation performed on plaster-immobilized-induced knee osteoarthritis rats. Based on the preliminary results, it suggested that the efficacy of the method relied on the reduction of inflammation and cartilage loss.

Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its ...

Treating Knee Osteoarthritis with Tuina in a Rabbit Model

Tuina Intervention in Rabbit Model of Knee Osteoarthritis

Knee osteoarthritis (KOA) is mainly characterized by degenerative changes in the knee joint's cartilage and surrounding soft tissues. The efficacy of Tuina in treating KOA has been confirmed, but the underlying mechanism needs to be investigated. This study aims to establish a scientifically feasible KOA rabbit model treated with Tuina to reveal the underlying mechanisms. For this, 18, 6-month-old normal-grade male New Zealand rabbits were randomly divided into sham, model, and Tuina groups, with 6 rabbits in each group. The KOA model was established by injecting 4% papain solution into the knee joint cavity. The Tuina group was intervened with Tuina combined with the knee joint rotary correction method for 4 weeks. Only the standard grasping and fixation were performed in sham and model groups. At the end of the 1-week intervention, the knee joint range of motion (ROM) was observed, and cartilage hematoxylin-eosin (HE) staining was done. The study shows that Tuina could inhibit chondrocyte apoptosis, repair cartilage tissue, and restore knee joint ROM. In conclusion, this study demonstrates the scientific feasibility of Tuina treatment for KOA model rabbits, highlighting its potential application in the study of KOA and similar knee joint-related conditions.

Author Spotlight: Using a Rabbit Model to Explore the Efficacy of Tuina in Treating Knee Osteoarthritis 

The protocol describes a method for Tuina intervention in a rabbit model of knee osteoarthritis.

Knee osteoarthritis (KOA) is mainly characterized by degenerative changes in the knee joint's cartilage and surrounding soft tissues. The efficacy of ...

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

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