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Unilateral intra-articular administration of a chondrocyte glycolytic inhibitor monoiodoacetate, was used to induce knee joint osteoarthritis in Sprague-Dawley rats. In this osteoarthritis model, histologically erosive disintegration of the articular surfaces of the ipsilateral joint are observed which closely mimic the clinical picture of osteoarthritis. Movement-induced pain behavior was measured using hind limb compressive grip force evaluation. The animals exhibited pain behaviors epitomized by a long-lasting decrement in bilateral compressive hind limb grip force following unilateral knee injury. The effects of clinically used reference analgesics were evaluated 20 days following i.a. injection of monoiodoacetate. Full analgesic activity was observed for tramadol, celecoxib and diclofenac; moderate effects for indomethacin, duloxetine and gabapentin but weak or no effects for acetaminophen, ibuprofen and lamotrigine. As morphine reduced grip force in naïve rats, its analgesic effects could not be accurately evaluated in this model. Finally, the effects of celecoxib were maintained following chronic dosing. The results indicate that this in vivo model utilizing a movement-induced pain behavior spawned by knee joint osteoarthritis may provide a valuable tool in examining the role of potential analgesic targets in osteoarthritic pain. As the model is clinically relevant, it will further enhance the mechanistic understanding of chronic arthritic joint pain and help in developing newer and better therapeutic strategies to manage osteoarthritis pain.", "publicationTitle": "European Journal of Pharmacology", "publisher": "", "place": "", "date": "June 24, 2009", "volume": "613", "issue": "1-3", "section": "", "partNumber": "", "partTitle": "", "pages": "39-45", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1016/j.ejphar.2009.04.009", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/B6T1J-4W32KS0-3/2/c03b2cdce83d19191cb8cabee416a5f2", "accessDate": "2011-04-07T23:09:14Z", "PMID": "", "PMCID": "", "ISSN": "0014-2999", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Animal model", "type": 1 }, { "tag": "OSTEOARTHRITIS", "type": 1 }, { "tag": "Pain", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2011-04-07T23:09:14Z", "dateModified": "2011-04-07T23:09:14Z" } }, { "key": "B96B7UHS", "version": 1, "library": { "type": "group", "id": 21160, "name": "Rat Research", "links": { "alternate": { "href": "https://www.zotero.org/groups/rat_research", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/21160/items/B96B7UHS", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/rat_research/items/B96B7UHS", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/21160/items/6FPXNTZR", "type": "application/json" } }, "meta": { "createdByUser": { "id": 45460, "username": "jessefrechette", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jessefrechette", "type": "text/html" } } } }, "data": { "key": "B96B7UHS", "version": 1, "parentItem": "6FPXNTZR", "itemType": "attachment", "linkMode": "imported_url", "title": "Snapshot", "accessDate": "2011-04-07T23:08:30Z", "url": "http://ard.bmj.com/content/51/8/932.short", "note": "", "contentType": "text/html", "charset": "utf-8", "filename": "932.html", "md5": null, "mtime": 1302217710180, "tags": [], "relations": {}, "dateAdded": "2011-04-07T23:08:30Z", "dateModified": "2011-04-07T23:09:00Z" } }, { "key": "6FPXNTZR", "version": 1, "library": { "type": "group", "id": 21160, "name": "Rat Research", "links": { "alternate": { "href": "https://www.zotero.org/groups/rat_research", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/21160/items/6FPXNTZR", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/rat_research/items/6FPXNTZR", "type": "text/html" } }, "meta": { "createdByUser": { "id": 45460, "username": "jessefrechette", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jessefrechette", "type": "text/html" } } }, "creatorSummary": "Schouten et al.", "parsedDate": "1992", "numChildren": 1 }, "data": { "key": "6FPXNTZR", "version": 1, "itemType": "journalArticle", "title": "A 12 year follow up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee.", "creators": [ { "creatorType": "author", "firstName": "J S", "lastName": "Schouten" }, { "creatorType": "author", "firstName": "F A", "lastName": "van den Ouweland" }, { "creatorType": "author", "firstName": "H A", "lastName": "Valkenburg" } ], "abstractNote": "The natural history and prognostic factors of cartilage loss in osteoarthritis of the knee were studied in subjects from a general population survey on rheumatic diseases in 1975-8. Baseline data were collected by questionnaire, physical examination, and weightbearing anteroposterior knee radiographs. Follow up of the subjects aged 46-68 years with radiological osteoarthritis grade 2-4 (Kellgren) took place in 1988-9. Cartilage loss was assessed by two observers who scored the change in joint space width between two radiographs. Thirty four per cent had cartilage loss. Prognostic factors and adjusted odds ratios (ORs) (95% confidence intervals) were: body mass index OR = 11.1 (3.3 to 37.3) fourth v first quartile; body weight OR = 7.9 (2.6 to 24.0) third v first tertile; age OR = 3.8 (1.1 to 13.4) > 60 v < or = 49 years; Heberden's nodes OR = 6.0 (1.5 to 23.1); clinical diagnosis of generalised osteoarthritis OR = 3.3 (1.3 to 8.3); and previous bow legs or knock knees OR = 5.1 (1.1 to 23.1). The relation of age with cartilage loss was also confounded by the presence of Heberden's nodes or a diagnosis of generalised osteoarthritis. There was no statistically significant relation for gender, meniscectomy, injury, uric acid concentration, chondrocalcinosis, smoking, and occupation related factors, except possibly standing.", "publicationTitle": "Annals of the Rheumatic Diseases", "publisher": "", "place": "", "date": "1992", "volume": "51", "issue": "8", "section": "", "partNumber": "", "partTitle": "", "pages": "932 -937", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1136/ard.51.8.932", "citationKey": "", "url": "http://ard.bmj.com/content/51/8/932.abstract", "accessDate": "2011-04-07T23:08:28Z", "PMID": "", "PMCID": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "Highwire 2.0", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2011-04-07T23:08:28Z", "dateModified": "2011-04-07T23:08:28Z" } }, { "key": "76TN7EU8", "version": 1, "library": { "type": "group", "id": 21160, "name": "Rat Research", "links": { "alternate": { "href": "https://www.zotero.org/groups/rat_research", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/21160/items/76TN7EU8", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/rat_research/items/76TN7EU8", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/21160/items/6PQQME8B", "type": "application/json" } }, "meta": { "createdByUser": { "id": 45460, "username": "jessefrechette", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jessefrechette", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "76TN7EU8", "version": 1, "parentItem": "6PQQME8B", "itemType": "note", "note": "

Accession Number: 2010439600. Language: English. Entry Date: 20100115. Revision Date: 20100115. Publication Type: journal article; research. Journal Subset: Biomedical; Peer Reviewed; USA. NLM UID: 0370605.

", "tags": [], "relations": {}, "dateAdded": "2011-04-07T23:04:33Z", "dateModified": "2011-04-07T23:04:33Z" } }, { "key": "6PQQME8B", "version": 1, "library": { "type": "group", "id": 21160, "name": "Rat Research", "links": { "alternate": { "href": "https://www.zotero.org/groups/rat_research", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/21160/items/6PQQME8B", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/rat_research/items/6PQQME8B", "type": "text/html" } }, "meta": { "createdByUser": { "id": 45460, "username": "jessefrechette", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jessefrechette", "type": "text/html" } } }, "creatorSummary": "Bar-Yehuda et al.", "parsedDate": "2009-10", "numChildren": 1 }, "data": { "key": "6PQQME8B", "version": 1, "itemType": "journalArticle", "title": "Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.", "creators": [ { "creatorType": "author", "firstName": "S", "lastName": "Bar-Yehuda" }, { "creatorType": "author", "firstName": "L", "lastName": "Rath-Wolfson" }, { "creatorType": "author", "firstName": "L", "lastName": "Del Valle" }, { "creatorType": "author", "firstName": "A", "lastName": "Ochaion" }, { "creatorType": "author", "firstName": "S", "lastName": "Cohen" }, { "creatorType": "author", "firstName": "R", "lastName": "Patoka" }, { "creatorType": "author", "firstName": "G", "lastName": "Zozulya" }, { "creatorType": "author", "firstName": "F", "lastName": "Barer" }, { "creatorType": "author", "firstName": "E", "lastName": "Atar" }, { "creatorType": "author", "firstName": "S", "lastName": "Pina-Oviedo" }, { "creatorType": "author", "firstName": "G", "lastName": "Perez-Liz" }, { "creatorType": "author", "firstName": "D", "lastName": "Castel" }, { "creatorType": "author", "firstName": "P", "lastName": "Fishman" } ], "abstractNote": "OBJECTIVE: Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. METHODS: OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 mug/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 mug/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. RESULTS: CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CONCLUSION: CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.", "publicationTitle": "Arthritis & Rheumatism", "publisher": "", "place": "", "date": "October 2009", "volume": "60", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "3061-3071", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "ARTHRITIS RHEUM", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0004-3591", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "EBSCOhost", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Adenosine -- Adverse Effects", "type": 1 }, { "tag": "Adenosine -- Analogs and Derivatives", "type": 1 }, { "tag": "Adenosine -- Pharmacodynamics", "type": 1 }, { "tag": "Adenosine -- Therapeutic Use", "type": 1 }, { "tag": "Animal Studies", "type": 1 }, { "tag": "Antiinflammatory Agents -- Adverse Effects", "type": 1 }, { "tag": "Antiinflammatory Agents -- Pharmacodynamics", "type": 1 }, { "tag": "Antiinflammatory Agents -- Therapeutic Use", "type": 1 }, { "tag": "Apoptosis -- Drug Effects", "type": 1 }, { "tag": "Apoptosis -- Physiology", "type": 1 }, { "tag": "Cartilage, Articular -- Drug Effects", "type": 1 }, { "tag": "Cartilage, Articular -- Metabolism", "type": 1 }, { "tag": "Cartilage, Articular -- Pathology", "type": 1 }, { "tag": "Inflammation -- Drug Therapy", "type": 1 }, { "tag": "Inflammation -- Metabolism", "type": 1 }, { "tag": "Inflammation -- Pathology", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Models, Biological", "type": 1 }, { "tag": "Osteoarthritis -- Chemically Induced", "type": 1 }, { "tag": "Osteoarthritis -- Drug Therapy", "type": 1 }, { "tag": "Osteoarthritis -- Pathology", "type": 1 }, { "tag": "Proteins -- Metabolism", "type": 1 }, { "tag": "Rats", "type": 1 }, { "tag": "Receptors, Cell Surface -- Antagonists and Inhibitors", "type": 1 }, { "tag": "Signal Transduction -- Drug Effects", "type": 1 }, { "tag": "Signal Transduction -- Physiology", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2011-04-07T23:04:33Z", "dateModified": "2011-04-07T23:04:33Z" } }, { "key": "RMFPTF78", "version": 1, "library": { "type": "group", "id": 21160, "name": "Rat Research", "links": { "alternate": { "href": "https://www.zotero.org/groups/rat_research", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/21160/items/RMFPTF78", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/rat_research/items/RMFPTF78", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/21160/items/Z9TRCNT3", "type": "application/json" } }, "meta": { "createdByUser": { "id": 45460, "username": "jessefrechette", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/jessefrechette", "type": "text/html" } } }, "lastModifiedByUser": { "id": 46901, "username": "janic141", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/janic141", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "RMFPTF78", "version": 1, "parentItem": "Z9TRCNT3", "itemType": "note", "note": "

Accession Number: 18925748; Source Info: Nov/Dec2005, Vol. 143 Issue 3, p71; Subject Term: AEROBIC exercises; Subject Term: OSTEOARTHRITIS; Subject Term: CLINICAL trials; Subject Term: PAIN; Subject Term: EXERCISE; Subject Term: RESPIRATION; Number of Pages: 1/2p; Document Type: Article; Full Text Word Count: 299

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Accession Number: 12067756.  Language: English. Date Revised: 20061115. Date Created: 20020617. Date Completed: 20030325. Update Code: 20101124. Publication Type: Journal Article; Research Support, Non-U.S. Gov't. Journal ID: 7910006. Publication Model: Print. Cited Medium: Print. NLM ISO Abbr: Immunol. Lett. Linking ISSN: 01652478. Subset: IM. Date of Electronic Publication: 20020902

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Language: English. Entry Date: 20051007. Revision Date: 20091218. Publication Type: journal article; research; tables/charts. Journal Subset: Biomedical; Double Blind Peer Reviewed; Expert Peer Reviewed; Online/Print; Peer Reviewed; USA. Special Interest: Perioperative Care. No. of Refs: 15 ref. 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Accession Number: 13918399; Tardif, Ginette 1 Reboul, Pascal 1 Pelletier, Jean-Pierre 1 Martel-Pelletier, Johanne 1; Email Address: jm@martelpelletier.ca; Affiliation:  1: Osteoarthritis Research Unit, Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada; Source Info: Jul2004, Vol. 14 Issue 3, p197; Subject Term: ARTHRITIS; Subject Term: CANCER; Subject Term: CARTILAGE; Subject Term: COLLAGENASES; Subject Term: METALLOPROTEINASES; Author-Supplied Keyword: Arthritis; Author-Supplied Keyword: Cancer; Author-Supplied Keyword: Cartilage; Author-Supplied Keyword: Collagenase-3; Author-Supplied Keyword: Matrix metalloproteinase (MMP)-13; Number of Pages: 8p; Document Type: Article

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Accession Number: 16720377.  Language: English. Date Revised: 20061115. Date Created: 20060524. Date Completed: 20060627. Update Code: 20101124. Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review. Journal ID: 9709506. Publication Model: Electronic. Cited Medium: Internet. NLM ISO Abbr: Front. Biosci. Linking ISSN: 10934715. Subset: IM. Date of Electronic Publication: 2006 Sep 01

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Accession Number: 2009934627. Language: English. Entry Date: 20080704. Revision Date: 20091218. Publication Type: journal article; research. Journal Subset: Biomedical; Peer Reviewed; USA. NLM UID: 0370605.

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Accession Number: 11566196; Pratta, Michael A. 1; Email Address: michael_a_pratta@gsk.com Wenqing Yao 1,2 Decicco, Carl 1 Tortorella, Micky D. 1,3 Riu-Qin Liu, Micky D. 1 Copeland, Robert A. 1 Magolda, Ronald 1,4 Newton, Robert C. 1,2 Trzaskos, James M. 1 Arner, Elizabeth C. 1,3; Affiliation:  1: Bristol Myers-Squibb Pharmaceutical Company, Delaware  2: Incyte Genomics, DE  3: Arthritis, Inflammation and Pain, Pfizer Discovery Research, IL  4: Department of Chemical and Screening Sciences, Wyeth Research, NJ; Source Info: 11/14/2003, Vol. 278 Issue 46, p45539; Subject Term: CARTILAGE; Subject Term: COLLAGEN; Subject Term: PROTEOLYSIS; Number of Pages: 7p; Illustrations: 3 Diagrams, 1 Chart, 12 Graphs; Document Type: Article

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Accession Number: 2002041909. Language: English. Entry Date: 20020419. Revision Date: 20091218. Publication Type: journal article; CEU; clinical trial; research; tables/charts. Commentary: McCormack R. Sport medicine journal club. Prevention of disability in daily activities in older persons with knee osteoarthritis. CLIN J SPORT MED 2002 Nov; 12(6): 405 (commentary) . Journal Subset: Biomedical; Peer Reviewed; USA. Special Interest: Evidence-Based Practice; Gerontologic Care. Grant Information: Supported by grant P60AG10484-01 from the National Institute on Aging, Bethesda, MD (Claude D. Pepper Older Americans Independence Center of Wake Forest University, Winston-Salem, NC); by grant M01-RR00211 from the General Clinical Research Center, Winston-Salem; and by the Brookdale Foundation, New York, NY. No. of Refs: 41 ref. NLM UID: 0372440.

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Accession Number: 2009334590. Language: English. Entry Date: 20070803. Revision Date: 20091218. Publication Type: journal article; clinical trial; research; tables/charts. Journal Subset: Biomedical; Peer Reviewed; USA. Special Interest: Public Health. Grant Information: NIH grants 5U01-AR-50901-02, 5P01-AI-40682-08, 1R01-AG-05407, and 1R01-AR-40431; the Doris Duke Clinical Research Fellowship Program for Medical Students (grant #20000684); the Rosalind Russell Arthritis Research Foundation; Roche Molecular Systems. No. of Refs: 38 ref. NLM UID: 0370605.

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Accession Number: 2009371097. Language: English. Entry Date: 20070202. Revision Date: 20081219. Publication Type: journal article; review; tables/charts. Journal Subset: Allied Health; Peer Reviewed; USA. Special Interest: Physical Therapy; Sports Medicine. No. of Refs: 27 ref. NLM UID: 9102787. Email: Pamela.Hansen@hsc.utah.edu

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