Name: rat model of adhesive capsulitis of the shoulder
Uploaded: 2018-09-28T14:00:00
Description: Watch this Scientific Journal Video about Rat Model of Adhesive Capsulitis of the Shoulder at JoVE.com

The Authors would like to acknowledge Mr. and Mrs. Tom and Phyllis Froeschle for providing financial support towards this project.

The study was approved by the Institutional Animal Care and Use Committee at Beth Israel Deaconess Medical Center. Care was taken to avoid unnecessary prolonged anesthesia and also to avoid hypothermia. Animals were weighted at each ROM measurement session and monitored for weight loss.
1. Study Subjects
<ol>
	<li>Use 10 Sprague-Dawley rats that are 13 weeks old at the time of surgery and that range between 250&#8211;300 g of body weight.</li>
</ol>
2. Surgical Procedur...

<ol>
	<li>Bunker, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+for+a+new+name+for+'frozen+shoulder'.">Time for a new name for 'frozen shoulder'.</a> British medical journal. 290 (6477), 1233-1234 (1985).</li><li>Bunker, T. D., Anthony, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathology+of+frozen+shoulder.+A+Dupuytren-like+disease.">The pathology of frozen shoulder. A Dupuytren-like disease.</a> The Journal of bone and joint surgery. British volume. 77 (5), 677-683 (1995).</li><li>Kilian, O., 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+frozen+shoulder.+Arthroscopy,+histological+findings+and+transmission+electron+microscopy+imaging.">The frozen shoulder. Arthroscopy, histological findings and transmission electron microscopy imaging.</a> Chirurg. 72 (11), 1303-1308 (2001).</li><li>Wang, 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=Risk+factors+in+idiopathic+adhesive+capsulitis:+a+case+control+study.">Risk factors in idiopathic adhesive capsulitis: a case control study.</a> Journal of Shoulder and Elbow Surgery. 22 (7), e24-e29 (2013).</li><li>Milgrom, 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=Risk+factors+for+idiopathic+frozen+shoulder.">Risk factors for idiopathic frozen shoulder.</a> The Israel Medical Association Journal. 10 (5), 361-364 (2008).</li><li>Huang, S. 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=Hyperthyroidism+is+a+risk+factor+for+developing+adhesive+capsulitis+of+the+shoulder:+a+nationwide+longitudinal+population-based+study.">Hyperthyroidism is a risk factor for developing adhesive capsulitis of the shoulder: a nationwide longitudinal population-based study.</a> Scientific Reports. 4, 4183 (2014).</li><li>Struyf, F., Meeus, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+evidence+on+physical+therapy+in+patients+with+adhesive+capsulitis:+what+are+we+missing.">Current evidence on physical therapy in patients with adhesive capsulitis: what are we missing.</a> Clinical Rheumatology. 33 (5), 593-600 (2014).</li><li>Song, A., Higgins, L. D., Newman, J., Jain, N. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glenohumeral+corticosteroid+injections+in+adhesive+capsulitis:+a+systematic+search+and+review.">Glenohumeral corticosteroid injections in adhesive capsulitis: a systematic search and review.</a> Journal Of Physical Medicine And Rehabilitation. 6 (12), 1143-1156 (2014).</li><li>Schollmeier, G., Sarkar, K., Fukuhara, K., Uhthoff, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Structural+and+functional+changes+in+the+canine+shoulder+after+cessation+of+immobilization.">Structural and functional changes in the canine shoulder after cessation of immobilization.</a> Clinical Orthopaedics and Related Research. 323 (323), 310-315 (1996).</li><li>Kanno, A., Sano, H., Itoi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+shoulder+contracture+model+in+rats.">Development of a shoulder contracture model in rats.</a> Journal of Shoulder and Elbow Surgery. 19 (5), 700-708 (2010).</li><li>Villa-Camacho, J. 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=In+vivo+kinetic+evaluation+of+an+adhesive+capsulitis+model+in+rats.">In vivo kinetic evaluation of an adhesive capsulitis model in rats.</a> Journal of Shoulder and Elbow Surgery. 24 (11), 1809-1816 (2015).</li><li>Liu, 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=Evaluation+of+Decalcification+Techniques+for+Rat+Femurs+Using+HE+and+Immunohistochemical+Staining.">Evaluation of Decalcification Techniques for Rat Femurs Using HE and Immunohistochemical Staining.</a> BioMed Research International. 2017, 9050754 (2017).</li><li>Gonzalez-Chavez, S. A., Pacheco-Tena, C., Macias-Vazquez, C. E., Luevano-Flores, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+different+decalcifying+protocols+on+Osteopontin+and+Osteocalcin+immunostaining+in+whole+bone+specimens+of+arthritis+rat+model+by+confocal+immunofluorescence.">Assessment of different decalcifying protocols on Osteopontin and Osteocalcin immunostaining in whole bone specimens of arthritis rat model by confocal immunofluorescence.</a> International Journal of Clinical and Experimental Pathology. 6 (10), 1972-1983 (2013).</li><li>Sanjai, 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=Evaluation+and+comparison+of+decalcification+agents+on+the+human+teeth.">Evaluation and comparison of decalcification agents on the human teeth.</a> Journal of Oral and Maxillofacial Pathology. 16 (2), 222-227 (2012).</li><li>Rolls, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> An Introduction to Decalcification. , (2013).</li><li>Burry, R. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controls+for+immunocytochemistry:+an+update.">Controls for immunocytochemistry: an update.</a> Journal of Histochemistry &amp; Cytochemistry. 59 (1), 6-12 (2011).</li><li>Sarver, J. 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=After+rotator+cuff+repair,+stiffness--but+not+the+loss+in+range+of+motion--increased+transiently+for+immobilized+shoulders+in+a+rat+model.">After rotator cuff repair, stiffness--but not the loss in range of motion--increased transiently for immobilized shoulders in a rat model.</a> Journal of Shoulder and Elbow Surgery. 17 (1 Suppl), 108S-113S (2008).</li><li>. Variations within Outbred Strains: Know Your Strains and Stocks | Taconic Biosciences Available from: <a target="_blank" href="https://www.taconic.com/taconic-insights/quality/variations-within-outbred-strains-know-your-strains-and-stocks.html">https://www.taconic.com/taconic-insights/quality/variations-within-outbred-strains-know-your-strains-and-stocks.html</a> (2016)</li><li>Liu, Y. L., Ao, Y. F., Cui, G. Q., Zhu, J. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+of+histology+and+capsular+collagen+in+a+rat+shoulder+immobilization+model.">Changes of histology and capsular collagen in a rat shoulder immobilization model.</a> Chinese Medical Journal. 124 (23), 3939-3944 (2011).</li></ol>

This study presents a rat model of adhesive capsulitis of the shoulder through internal fixation of the glenohumeral joint. Furthermore, it shows an extended reduction of total ROM for at least 8 weeks after removal of the fixation. In order to calculate the alterations in ROM at different time points, measurements were compared to animal specific baselines. Conversely, Kanno et al.10&#160;used a standardized torque for all of the animals in order to determine ex vivo ROM changes...

Adhesive capsulitis of the shoulder is frequently referred to as frozen shoulder or shoulder contracture. It is characterized by restricted glenohumeral motion and pain, presumably as a result of advanced fibrosis and joint contracture1,2,3. The condition involves fibroblast and myofibroblast cell recruitment with a resultant dense collagen matrix (types I and III) in the joint capsule2,3. There are many possible risk factors for developing a joint contracture, including gender, diabetes mellitus, hyperthyroidism, traumatic injury, and prolonged immobilization4,5,6.
Effective treatment options are lacking and mostly include physical therapy, with intervention in the form of surgical release in extreme cases that have not improved with conservative care. The best treatment method remains undetermined and has been a subject of great interest for years in the medical field7,8. Development of novel therapeutic options will require a reproducible animal model for the condition that does not rely on intra-articular induced trauma. The optimal adhesive capsulitis model should involve the two main characteristics of the disease: contracture of the shoulder capsule and a prolonged reduction in range of motion (ROM). Schollmeier et al.9 described one of the first joint contracture models by using a cast to develop shoulder contracture in canines. They also reported that changes in ROM and intra-articular pressure returned to normal levels after cessation of immobilization9. However, an important limitation mentioned in the study is the variation in limb position between animals because of the use of a cast technique.In order to obtain a more reproducible model, Kanno et al.10 later presented an adhesive capsulitis rat model using rigid internal fixation of the shoulder. However, although they achieved a significant reduction in ROM with their model, they did not state whether these changes were temporary or long lasting. The aim of our study was to create a suitable in vivo shoulder contracture rat model by investigating the effect of prolonged extra-articular glenohumeral joint immobilization on ROM and joint stiffness.

<table>
	<tbody>
		<tr>
			<td>Sprague-Dawley rats</td>
			<td>Charles River Laboratories, Wilmington, MA, USA</td>
			<td></td>
			<td>250-300 g</td>
		</tr>
		<tr>
			<td>Surgical tool:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Injection needle</td>
			<td></td>
			<td></td>
			<td>BD 1&#39; 30 guage</td>
		</tr>
		<tr>
			<td>Needle holder</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>5% isoflurane</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>2% isoflurane</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nose cone</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Skalpel and skalpel holder</td>
			<td></td>
			<td></td>
			<td>No. 11 scalpel</td>
		</tr>
		<tr>
			<td>Curved hemostat forceps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Staright hemostat forceps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tissue retractor</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Toothed tissue forceps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Plain tissue forceps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dissecting scissors</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Suture scissors</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Skin clip applicator</td>
			<td></td>
			<td></td>
			<td>Any standard staples for wound closure</td>
		</tr>
		<tr>
			<td>Immobilization material</td>
			<td>Ethicon</td>
			<td></td>
			<td>No. 2-0 braided polyester ethibond suture was used for immobilization</td>
		</tr>
		<tr>
			<td>Other materials:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Costumized device for ROM: 1)Sensor assembly, 2)pivoting axle, 3)arm clamp</td>
			<td></td>
			<td></td>
			<td>Assembly that is described in relaxin paper and adhesive capsulitis paper</td>
		</tr>
		<tr>
			<td>Orientation sensor (part of sensor assembly)</td>
			<td>MicroStrain Inc., Williston, VT, USA</td>
			<td></td>
			<td>3DM-GX3-15</td>
		</tr>
		<tr>
			<td>Reaction torque sensor (part of sensor assembly)</td>
			<td>Futek Inc., Irvine, CA, USA</td>
			<td></td>
			<td>TFF400</td>
		</tr>
		<tr>
			<td>Stepper Motor</td>
			<td>SparkFun Electronics, Niwot, CO 80503</td>
			<td></td>
			<td>https://www.sparkfun.com/products/13656</td>
		</tr>
		<tr>
			<td>Microcontroller</td>
			<td>Torino, Italy).</td>
			<td></td>
			<td>Arduino UNO, R3</td>
		</tr>
		<tr>
			<td>MATLAB code</td>
			<td>MATLAB 7.13.0.564, Natick, Ma, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Weight Scale</td>
			<td></td>
			<td></td>
			<td>Ohaus</td>
		</tr>
	</tbody>
</table>

rat model of adhesive capsulitis of the shoulder

This proposal aims to create an in vivo rat model of adhesive capsulitis for researching potential treatment options for this condition and other etiologies of comparable arthrofibrosis. The model includes extra-articular fixation of the shoulder in rats via scapular to humeral suturing, resulting in a secondary contracture without invading the intra-articular space and resulting in decreased rotational ROM and increased joint stiffness.
We used 10 Sprague-Dawley rats for the purpose of this study. Baseline ROM measurements were taken before glenohumeral immobilization. The rats were subjected to 8 weeks of immobilization before the fixation sutures were removed and changes in ROM and joint stiffness were evaluated. To evaluate whether immobilization resulted in a significant reduction in ROM, changes in kinematics were calculated. ROM was measured at each time point in the follow-up period and was compared to the baseline internal and external ROM measurements. In order to evaluate the stiffness, joint kinetics were calculated by determining the differences in torque (text and tint ) needed to reach the initial external rotation of 60&#176; and initial internal rotation of 80&#176;.
After the removal of the extra-articular suture fixation on follow-up day 0, we found a 63% decrease in total ROM compared to baseline. We observed continuous improvement until week 5 of follow-up, with the progress slowing down around a 19% restriction. On week 8 of follow-up, there was still an 18% restriction of ROM. Additionally, on follow-up day 0, we found the torque increased by 13.3 Nmm when compared to baseline. On week 8, the total torque was measured to be 1.4 &#177; 0.2 Nmm higher than initial measurements. This work introduces a rat model of shoulder adhesive capsulitis with lasting reduced ROM and increased stiffness.

Range of motion
On follow-up day 0, we found a 63% decrease in total ROM compared to baseline (P &#60; .001). We observed a gradual improvement of ROM until week 5 of follow-up, when progression stopped at 19% restriction (P &#60;0.001). The remaining restriction, 18% of total ROM, was still apparent at 8 weeks of follow-up (P &#60;0.001).
Stiffness
<p class="jove_conten...

Watch this Scientific Journal Video about Rat Model of Adhesive Capsulitis of the Shoulder at JoVE.com

Rat Model of Adhesive Capsulitis of the Shoulder

This protocol presents an in vivo rat model of adhesive capsulitis. The model includes an internal fixation of the glenohumeral joint with extra-articular suture fixation for an extended time, resulting in a decreased rotational range of motion (ROM) and increased joint stiffness.

This proposal aims to create an in vivo rat model of adhesive capsulitis for researching potential treatment options for this condition and other ...

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