{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:51:02Z","timestamp":1791442262473,"version":"4.3.3"},"reference-count":162,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a highly prevalent and disabling disease, with pain as its most debilitating symptom. Despite extensive preclinical research, no therapy has successfully translated from animal models into routine clinical use. Commonly used animal models (e.g., acute, surgically, or chemically induced OA in young, single-sex animals) often fail to reflect the chronic and multifactorial human condition, which is often seen in older, postmenopausal women with comorbidities and mixed nociceptive\u2013neuropathic pain. This review aims to identify animal models and pain assessment methods for predicting drug efficacy in OA pain management and to examine the translational gap, focusing on pain as a primary endpoint in animal and human clinical studies. Ultimately, we emphasize the need for phenotype-specific, clinically relevant models to improve translational validity and accelerate the development of effective OA pain therapies.<\/jats:p>","DOI":"10.1038\/s43856-026-01926-7","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:13:16Z","timestamp":1791439996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the translational value of animal models in developing pain-targeting therapies for clinical osteoarthritis"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-8892","authenticated-orcid":false,"given":"Alexandra","family":"Stubelius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-7394","authenticated-orcid":false,"given":"Cecilia","family":"Aulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9635-6893","authenticated-orcid":false,"given":"Luminita","family":"Labusca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Kontogiorgis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2837-9967","authenticated-orcid":false,"given":"Gina","family":"Lisignoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-1286","authenticated-orcid":false,"given":"Ali","family":"Mobasheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Nothnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"N\u00fcrnberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3679-2869","authenticated-orcid":false,"given":"Jaqueline Lourdes","family":"Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Sollmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Van den Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5152-9532","authenticated-orcid":false,"given":"Lucienne","family":"Vonk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Corciulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"1926_CR1","doi-asserted-by":"publisher","unstructured":"Ahluwalia, A. et al. What\u2019s in a NAM? Lab. Anim. https:\/\/doi.org\/10.1038\/s41684-026-01731-8 (2026).","DOI":"10.1038\/s41684-026-01731-8"},{"key":"1926_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/ilar\/ilab020","volume":"62","author":"LB Kinter","year":"2021","unstructured":"Kinter, L. B., DeHaven, R., Johnson, D. K. & DeGeorge, J. J. A brief history of use of animals in biomedical research and perspective on non-animal alternatives. ILAR J. 62, 7\u201316 https:\/\/doi.org\/10.1093\/ilar\/ilab020 (2021).","journal-title":"ILAR J."},{"key":"1926_CR3","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s43441-023-00509-1","volume":"57","author":"E Kim","year":"2023","unstructured":"Kim, E., Yang, J., Park, S. & Shin, K. Factors affecting success of new drug clinical trials. Ther. Innov. Regul. Sci. 57, 737\u2013750 https:\/\/doi.org\/10.1007\/s43441-023-00509-1 (2023).","journal-title":"Ther. Innov. Regul. Sci."},{"key":"1926_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103726","volume":"28","author":"A Schuhmacher","year":"2023","unstructured":"Schuhmacher, A., Hinder, M., von Stegmann Und Stein, A., Hartl, D. & Gassmann, O. Analysis of pharma R&D productivity\u2014a new perspective needed. Drug Discov. Today 28, 103726 https:\/\/doi.org\/10.1016\/j.drudis.2023.103726 (2023).","journal-title":"Drug Discov. Today"},{"key":"1926_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s41231-019-0050-7","volume":"4","author":"AA Seyhan","year":"2019","unstructured":"Seyhan, A. A. Lost in translation: the valley of death across preclinical and clinical divide \u2013 identification of problems and overcoming obstacles. Transl. Med. Commun. 4, 18 https:\/\/doi.org\/10.1186\/s41231-019-0050-7 (2019).","journal-title":"Transl. Med. Commun."},{"key":"1926_CR6","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.jpain.2017.12.261","volume":"19","author":"RP Yezierski","year":"2018","unstructured":"Yezierski, R. P. & Hansson, P. Inflammatory and neuropathic pain from bench to bedside: what went wrong?. J. Pain. 19, 571\u2013588 https:\/\/doi.org\/10.1016\/j.jpain.2017.12.261 (2018).","journal-title":"J. Pain."},{"key":"1926_CR7","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.rdc.2020.12.002","volume":"47","author":"AM Malfait","year":"2021","unstructured":"Malfait, A. M., Miller, R. E. & Miller, R. J. Basic mechanisms of pain in osteoarthritis: experimental observations and new perspectives. Rheum. Dis. Clin. North Am. 47, 165\u2013180 https:\/\/doi.org\/10.1016\/j.rdc.2020.12.002 (2021).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"1926_CR8","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.jpain.2013.06.008","volume":"14","author":"NS Gregory","year":"2013","unstructured":"Gregory, N. S. et al. An overview of animal models of pain: disease models and outcome measures. J. Pain. 14, 1255\u20131269 https:\/\/doi.org\/10.1016\/j.jpain.2013.06.008 (2013).","journal-title":"J. Pain."},{"key":"1926_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1833313","volume":"17","author":"M Yan","year":"2026","unstructured":"Yan, M. et al. From mechanical triggering to metabolic-inflammatory driving: a new paradigm of knee osteoarthritis pathogenesis. Front. Immunol. 17, 1833313. https:\/\/doi.org\/10.3389\/fimmu.2026.1833313 (2026).","journal-title":"Front. Immunol."},{"key":"1926_CR10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","volume":"11","author":"S Tang","year":"2025","unstructured":"Tang, S. et al. Osteoarthritis. Nat. Rev. Dis. Prim. 11, 10 https:\/\/doi.org\/10.1038\/s41572-025-00594-6 (2025).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"1926_CR11","first-page":"1513","volume":"27","author":"MT Hannan","year":"2000","unstructured":"Hannan, M. T., Felson, D. T. & Pincus, T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J. Rheumatol. 27, 1513\u20131517 (2000).","journal-title":"J. Rheumatol."},{"key":"1926_CR12","first-page":"75","volume":"35","author":"T Neogi","year":"2017","unstructured":"Neogi, T. Structural correlates of pain in osteoarthritis. Clin. Exp. Rheumatol. 35, 75\u201378 (2017).","journal-title":"Clin. Exp. Rheumatol."},{"key":"1926_CR13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1080\/03008207.2025.2531414","volume":"66","author":"DB Hoffman","year":"2025","unstructured":"Hoffman, D. B., Miller, R. E. & Malfait, A. M. Pain mechanisms in osteoarthritis: recent discoveries and opportunities ahead. Connect Tissue Res. 66, 359\u2013366 https:\/\/doi.org\/10.1080\/03008207.2025.2531414 (2025).","journal-title":"Connect Tissue Res."},{"key":"1926_CR14","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1097\/j.pain.0000000000000492","volume":"157","author":"NB Finnerup","year":"2016","unstructured":"Finnerup, N. B. et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain 157, 1599\u20131606 https:\/\/doi.org\/10.1097\/j.pain.0000000000000492 (2016).","journal-title":"Pain"},{"key":"1926_CR15","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.joca.2021.03.021","volume":"29","author":"L Zolio","year":"2021","unstructured":"Zolio, L. et al. Systematic review and meta-analysis of the prevalence of neuropathic-like pain and\/or pain sensitization in people with knee and hip osteoarthritis. Osteoarthr. Cartil. 29, 1096\u20131116 https:\/\/doi.org\/10.1016\/j.joca.2021.03.021 (2021).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR16","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s11684-025-1143-5","volume":"19","author":"L Li","year":"2025","unstructured":"Li, L. et al. Understanding pain heterogeneity in osteoarthritis patients: a narrative review. Front. Med. 19, 769\u2013788 https:\/\/doi.org\/10.1007\/s11684-025-1143-5 (2025).","journal-title":"Front. Med."},{"key":"1926_CR17","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.joca.2022.12.003","volume":"31","author":"A Kamps","year":"2023","unstructured":"Kamps, A. et al. Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands. Osteoarthr. Cartil. 31, 519\u2013528 https:\/\/doi.org\/10.1016\/j.joca.2022.12.003 (2023).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR18","doi-asserted-by":"publisher","DOI":"10.1177\/17448069251411647","volume":"22","author":"M Zhuo","year":"2026","unstructured":"Zhuo, M. Brain networking pain and anxiety: From basic mechanism to future treatment. Mol. Pain. 22, 17448069251411647 https:\/\/doi.org\/10.1177\/17448069251411647 (2026).","journal-title":"Mol. Pain."},{"key":"1926_CR19","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1002\/hbm.22105","volume":"34","author":"MT Tseng","year":"2013","unstructured":"Tseng, M. T., Chiang, M. C., Chao, C. C., Tseng, W. Y. & Hsieh, S. T. fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations. Hum. Brain Mapp. 34, 2733\u20132746 https:\/\/doi.org\/10.1002\/hbm.22105 (2013).","journal-title":"Hum. Brain Mapp."},{"key":"1926_CR20","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/j.1532-2149.2013.00388.x","volume":"18","author":"J Kemp","year":"2014","unstructured":"Kemp, J., Despres, O., Pebayle, T. & Dufour, A. Differences in age-related effects on myelinated and unmyelinated peripheral fibres: a sensitivity and evoked potentials study. Eur. J. Pain. 18, 482\u2013488 https:\/\/doi.org\/10.1002\/j.1532-2149.2013.00388.x (2014).","journal-title":"Eur. J. Pain."},{"key":"1926_CR21","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.joca.2018.09.016","volume":"27","author":"PJ Cope","year":"2019","unstructured":"Cope, P. J., Ourradi, K., Li, Y. & Sharif, M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthr. Cartil. 27, 230\u2013239 https:\/\/doi.org\/10.1016\/j.joca.2018.09.016 (2019).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR22","doi-asserted-by":"publisher","first-page":"e0239663","DOI":"10.1371\/journal.pone.0239663","volume":"15","author":"PRW Gowler","year":"2020","unstructured":"Gowler, P. R. W. et al. Refining surgical models of osteoarthritis in mice and rats alters pain phenotype but not joint pathology. PLoS ONE 15, e0239663 https:\/\/doi.org\/10.1371\/journal.pone.0239663 (2020).","journal-title":"PLoS ONE"},{"key":"1926_CR23","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1302\/2046-3758.73.BJR-2017-0121.R2","volume":"7","author":"T Tawonsawatruk","year":"2018","unstructured":"Tawonsawatruk, T., Sriwatananukulkit, O., Himakhun, W. & Hemstapat, W. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Jt. Res. 7, 244\u2013251 https:\/\/doi.org\/10.1302\/2046-3758.73.BJR-2017-0121.R2 (2018).","journal-title":"Bone Jt. Res."},{"key":"1926_CR24","doi-asserted-by":"publisher","unstructured":"Kloser, H., Henao-Tamayo, M. & Santangelo, K. S. A review of rodent behavior, mobility, and pain modifications in response to destabilization of the medial meniscus injury. Biomedicines 13 https:\/\/doi.org\/10.3390\/biomedicines13122886 (2025).","DOI":"10.3390\/biomedicines13122886"},{"key":"1926_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-024-08083-9","volume":"25","author":"Y Sasaki","year":"2024","unstructured":"Sasaki, Y., Kijima, K. & Yoshioka, K. Validity evaluation of a rat model of monoiodoacetate-induced osteoarthritis with clinically effective drugs. BMC Musculoskelet. Disord. 25, 975 https:\/\/doi.org\/10.1186\/s12891-024-08083-9 (2024).","journal-title":"BMC Musculoskelet. Disord."},{"key":"1926_CR26","doi-asserted-by":"publisher","first-page":"5507","DOI":"10.2147\/JPR.S527135","volume":"18","author":"M Song","year":"2025","unstructured":"Song, M. et al. Monosodium iodoacetate induces knee osteoarthritis in rats in a dose- and time-dependent manner. J. Pain Res. 18, 5507\u20135522 https:\/\/doi.org\/10.2147\/JPR.S527135 (2025).","journal-title":"J. Pain Res."},{"key":"1926_CR27","doi-asserted-by":"publisher","unstructured":"Pitcher, T., Sousa-Valente, J. & Malcangio, M. The monoiodoacetate model of osteoarthritis pain in the mouse. J. Vis. Exp. https:\/\/doi.org\/10.3791\/53746 (2016).","DOI":"10.3791\/53746"},{"key":"1926_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38282","volume":"10","author":"JP Martins","year":"2024","unstructured":"Martins, J. P. & Marson, F. A. L. A narrative review of the complex panorama regarding chronic neuropathic pain mainly for the psychological issues. Heliyon 10, e38282 https:\/\/doi.org\/10.1016\/j.heliyon.2024.e38282 (2024).","journal-title":"Heliyon"},{"key":"1926_CR29","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.joca.2022.01.010","volume":"30","author":"M Alves-Simoes","year":"2022","unstructured":"Alves-Simoes, M. Rodent models of knee osteoarthritis for pain research. Osteoarthr. Cartil. 30, 802\u2013814 https:\/\/doi.org\/10.1016\/j.joca.2022.01.010 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR30","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.neubiorev.2019.03.009","volume":"100","author":"A Tappe-Theodor","year":"2019","unstructured":"Tappe-Theodor, A., King, T. & Morgan, M. M. Pros and cons of clinically relevant methods to assess pain in rodents. Neurosci. Biobehav. Rev. 100, 335\u2013343 https:\/\/doi.org\/10.1016\/j.neubiorev.2019.03.009 (2019).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1926_CR31","doi-asserted-by":"publisher","first-page":"851","DOI":"10.2147\/JPR.S158847","volume":"11","author":"AH Alghadir","year":"2018","unstructured":"Alghadir, A. H., Anwer, S., Iqbal, A. & Iqbal, Z. A. Test-retest reliability, validity, and minimum detectable change of visual analog, numerical rating, and verbal rating scales for measurement of osteoarthritic knee pain. J. Pain Res. 11, 851\u2013856 https:\/\/doi.org\/10.2147\/JPR.S158847 (2018).","journal-title":"J. Pain Res."},{"key":"1926_CR32","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1186\/s13075-016-1151-6","volume":"18","author":"E Nikiphorou","year":"2016","unstructured":"Nikiphorou, E. et al. Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature. Arthritis Res. Ther. 18, 251 https:\/\/doi.org\/10.1186\/s13075-016-1151-6 (2016).","journal-title":"Arthritis Res. Ther."},{"key":"1926_CR33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1477-7525-1-17","volume":"1","author":"EM Roos","year":"2003","unstructured":"Roos, E. M. & Toksvig-Larsen, S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual. Life Outcomes 1, 17 https:\/\/doi.org\/10.1186\/1477-7525-1-17 (2003).","journal-title":"Health Qual. Life Outcomes"},{"key":"1926_CR34","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1097\/j.pain.0000000000000603","volume":"157","author":"LA Frey-Law","year":"2016","unstructured":"Frey-Law, L. A. et al. Pain sensitivity profiles in patients with advanced knee osteoarthritis. Pain 157, 1988\u20131999 https:\/\/doi.org\/10.1097\/j.pain.0000000000000603 (2016).","journal-title":"Pain"},{"key":"1926_CR35","doi-asserted-by":"publisher","unstructured":"Dias, P., Tavares, I., Fonseca, S. & Pozza, D. H. Outcomes of a QST protocol in healthy subjects and chronic pain patients: a controlled clinical trial. Biomedicines 11 https:\/\/doi.org\/10.3390\/biomedicines11041023 (2023).","DOI":"10.3390\/biomedicines11041023"},{"key":"1926_CR36","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","volume":"27","author":"RR Bannuru","year":"2019","unstructured":"Bannuru, R. R. et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr. Cartil. 27, 1578\u20131589 https:\/\/doi.org\/10.1016\/j.joca.2019.06.011 (2019).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR37","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1185\/03007995.2014.946123","volume":"30","author":"A Gibofsky","year":"2014","unstructured":"Gibofsky, A., Hochberg, M. C., Jaros, M. J. & Young, C. L. Efficacy and safety of low-dose submicron diclofenac for the treatment of osteoarthritis pain: a 12 week, phase 3 study. Curr. Med. Res. Opin. 30, 1883\u20131893 https:\/\/doi.org\/10.1185\/03007995.2014.946123 (2014).","journal-title":"Curr. Med. Res. Opin."},{"key":"1926_CR38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.pain.2004.08.004","volume":"112","author":"J Fernihough","year":"2004","unstructured":"Fernihough, J. et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain 112, 83\u201393 https:\/\/doi.org\/10.1016\/j.pain.2004.08.004 (2004).","journal-title":"Pain"},{"key":"1926_CR39","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ejphar.2009.04.009","volume":"613","author":"P Chandran","year":"2009","unstructured":"Chandran, P. et al. Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis. Eur. J. Pharm. 613, 39\u201345 https:\/\/doi.org\/10.1016\/j.ejphar.2009.04.009 (2009).","journal-title":"Eur. J. Pharm."},{"key":"1926_CR40","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.joca.2016.02.006","volume":"24","author":"S Ogawa","year":"2016","unstructured":"Ogawa, S. et al. Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate. Osteoarthr. Cartil. 24, 1190\u20131199 https:\/\/doi.org\/10.1016\/j.joca.2016.02.006 (2016).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR41","doi-asserted-by":"publisher","unstructured":"Galimberti, G. et al. Prokineticin system is a pharmacological target to counteract pain and its comorbid mood alterations in an osteoarthritis murine model. Cells 12 https:\/\/doi.org\/10.3390\/cells12182255 (2023).","DOI":"10.3390\/cells12182255"},{"key":"1926_CR42","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1089\/jmf.2016.0167","volume":"20","author":"M Yimam","year":"2017","unstructured":"Yimam, M. et al. A botanical composition mitigates cartilage degradations and pain sensitivity in osteoarthritis disease model. J. Med. Food 20, 568\u2013576 https:\/\/doi.org\/10.1089\/jmf.2016.0167 (2017).","journal-title":"J. Med. Food"},{"key":"1926_CR43","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1002\/art.40835","volume":"71","author":"F Ter Heegde","year":"2019","unstructured":"Ter Heegde, F. et al. Noninvasive mechanical joint loading as an alternative model for osteoarthritic pain. Arthritis Rheumatol. 71, 1078\u20131088 https:\/\/doi.org\/10.1002\/art.40835 (2019).","journal-title":"Arthritis Rheumatol."},{"key":"1926_CR44","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1124\/jpet.106.110387","volume":"319","author":"AM Pulichino","year":"2006","unstructured":"Pulichino, A. M. et al. Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis. J. Pharm. Exp. Ther. 319, 1043\u20131050 https:\/\/doi.org\/10.1124\/jpet.106.110387 (2006).","journal-title":"J. Pharm. Exp. Ther."},{"key":"1926_CR45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12906-021-03236-y","volume":"21","author":"M Mohammadifar","year":"2021","unstructured":"Mohammadifar, M. et al. Anti-osteoarthritis potential of peppermint and rosemary essential oils in a nanoemulsion form: behavioral, biochemical, and histopathological evidence. BMC Complement Med. Ther. 21, 57 https:\/\/doi.org\/10.1186\/s12906-021-03236-y (2021).","journal-title":"BMC Complement Med. Ther."},{"key":"1926_CR46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40199-016-0152-y","volume":"24","author":"A Ziaei","year":"2016","unstructured":"Ziaei, A., Sahranavard, S., Gharagozlou, M. J. & Faizi, M. Preliminary investigation of the effects of topical mixture of Lawsonia inermis L. and Ricinus communis L. leaves extract in treatment of osteoarthritis using MIA model in rats. Daru 24, 12 https:\/\/doi.org\/10.1186\/s40199-016-0152-y (2016).","journal-title":"Daru"},{"key":"1926_CR47","doi-asserted-by":"publisher","first-page":"e0346166","DOI":"10.1371\/journal.pone.0346166","volume":"21","author":"M Pan","year":"2026","unstructured":"Pan, M. et al. Study on the therapeutic effect of eggshell membrane on osteoarthritis in rats. PLoS ONE 21, e0346166 https:\/\/doi.org\/10.1371\/journal.pone.0346166 (2026).","journal-title":"PLoS ONE"},{"key":"1926_CR48","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1124\/jpet.110.167924","volume":"334","author":"E Yoshimi","year":"2010","unstructured":"Yoshimi, E. et al. Antinociceptive effects of AS1892802, a novel Rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis. J. Pharm. Exp. Ther. 334, 955\u2013963 https:\/\/doi.org\/10.1124\/jpet.110.167924 (2010).","journal-title":"J. Pharm. Exp. Ther."},{"key":"1926_CR49","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.pbb.2012.03.003","volume":"101","author":"J Ferreira-Gomes","year":"2012","unstructured":"Ferreira-Gomes, J., Adaes, S., Mendonca, M. & Castro-Lopes, J. M. Analgesic effects of lidocaine, morphine and diclofenac on movement-induced nociception, as assessed by the Knee-Bend and CatWalk tests in a rat model of osteoarthritis. Pharm. Biochem. Behav. 101, 617\u2013624 https:\/\/doi.org\/10.1016\/j.pbb.2012.03.003 (2012).","journal-title":"Pharm. Biochem. Behav."},{"key":"1926_CR50","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1124\/jpet.107.134510","volume":"325","author":"P Clark","year":"2008","unstructured":"Clark, P. et al. MF498 [N-[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis. J. Pharm. Exp. Ther. 325, 425\u2013434 https:\/\/doi.org\/10.1124\/jpet.107.134510 (2008).","journal-title":"J. Pharm. Exp. Ther."},{"key":"1926_CR51","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.ejphar.2014.05.048","volume":"738","author":"G Ishikawa","year":"2014","unstructured":"Ishikawa, G., Nagakura, Y., Takeshita, N. & Shimizu, Y. Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis. Eur. J. Pharm. 738, 111\u2013117 https:\/\/doi.org\/10.1016\/j.ejphar.2014.05.048 (2014).","journal-title":"Eur. J. Pharm."},{"key":"1926_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-022-05937-y","volume":"23","author":"T Arai","year":"2022","unstructured":"Arai, T. et al. Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model. BMC Musculoskelet. Disord. 23, 960 https:\/\/doi.org\/10.1186\/s12891-022-05937-y (2022).","journal-title":"BMC Musculoskelet. Disord."},{"key":"1926_CR53","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1185\/03007995.2015.1112772","volume":"31","author":"R Altman","year":"2015","unstructured":"Altman, R., Hochberg, M., Gibofsky, A., Jaros, M. & Young, C. Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: a 12-week, phase 3 study. Curr. Med. Res. Opin. 31, 2331\u20132343 https:\/\/doi.org\/10.1185\/03007995.2015.1112772 (2015).","journal-title":"Curr. Med. Res. Opin."},{"key":"1926_CR54","doi-asserted-by":"publisher","unstructured":"Khotib, J., Utami, N. W., Gani, M. A. & Ardianto, C. The change of proinflammatory cytokine tumor necrosis factor alpha level in the use of meloxicam in rat model of osteoarthritis. J. Basic Clin. Physiol. Pharmacol. 30 https:\/\/doi.org\/10.1515\/jbcpp-2019-0331 (2019).","DOI":"10.1515\/jbcpp-2019-0331"},{"key":"1926_CR55","doi-asserted-by":"publisher","unstructured":"Logashina, Y. A. et al. Anti-inflammatory and analgesic effects of TRPV1 polypeptide modulator APHC3 in models of osteo- and rheumatoid arthritis. Mar. Drugs 19 https:\/\/doi.org\/10.3390\/md19010039 (2021).","DOI":"10.3390\/md19010039"},{"key":"1926_CR56","doi-asserted-by":"publisher","unstructured":"Maleeva, E. E. et al. Potentiating TRPA1 by sea anemone peptide Ms 9a-1 reduces pain and inflammation in a model of osteoarthritis. Mar. Drugs 21 https:\/\/doi.org\/10.3390\/md21120617 (2023).","DOI":"10.3390\/md21120617"},{"key":"1926_CR57","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1097\/j.pain.0000000000003190","volume":"165","author":"LA Pattison","year":"2024","unstructured":"Pattison, L. A. et al. Digging deeper into pain: an ethological behavior assay correlating well-being in mice with human pain experience. Pain 165, 1761\u20131773 https:\/\/doi.org\/10.1097\/j.pain.0000000000003190 (2024).","journal-title":"Pain"},{"key":"1926_CR58","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1111\/1440-1681.13551","volume":"48","author":"FY Han","year":"2021","unstructured":"Han, F. Y., Brockman, D. A., Nicholson, J. R., Corradini, L. & Smith, M. T. Pharmacological characterization of the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis pain in the knee joint. Clin. Exp. Pharm. Physiol. 48, 1515\u20131522 https:\/\/doi.org\/10.1111\/1440-1681.13551 (2021).","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"1926_CR59","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.joca.2006.01.013","volume":"14","author":"RR Castro","year":"2006","unstructured":"Castro, R. R., Cunha, F. Q., Silva, F. S. Jr. & Rocha, F. A. A quantitative approach to measure joint pain in experimental osteoarthritis\u2013evidence of a role for nitric oxide. Osteoarthr. Cartil. 14, 769\u2013776 https:\/\/doi.org\/10.1016\/j.joca.2006.01.013 (2006).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR60","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1185\/03007995.2014.955169","volume":"30","author":"MC Yoo","year":"2014","unstructured":"Yoo, M. C. et al. Etoricoxib in the treatment of Korean patients with osteoarthritis in a double-blind, randomized controlled trial. Curr. Med. Res. Opin. 30, 2399\u20132408 https:\/\/doi.org\/10.1185\/03007995.2014.955169 (2014).","journal-title":"Curr. Med. Res. Opin."},{"key":"1926_CR61","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1093\/rheumatology\/kel296","volume":"46","author":"CO Bingham","year":"2007","unstructured":"Bingham, C. O. et al. Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies. Rheumatology 46, 496\u2013507 https:\/\/doi.org\/10.1093\/rheumatology\/kel296 (2007).","journal-title":"Rheumatology"},{"key":"1926_CR62","doi-asserted-by":"publisher","unstructured":"Sun, Q. et al. Inhibition of PGE2 in subchondral bone attenuates osteoarthritis. Cells 11 https:\/\/doi.org\/10.3390\/cells11172760 (2022).","DOI":"10.3390\/cells11172760"},{"key":"1926_CR63","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s11596-023-2725-6","volume":"43","author":"P Gao","year":"2023","unstructured":"Gao, P. et al. Tetrandrine represses inflammation and attenuates osteoarthritis by selective inhibition of COX-2. Curr. Med. Sci. 43, 505\u2013513 https:\/\/doi.org\/10.1007\/s11596-023-2725-6 (2023).","journal-title":"Curr. Med. Sci."},{"key":"1926_CR64","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.pain.2004.11.008","volume":"114","author":"JD Pomonis","year":"2005","unstructured":"Pomonis, J. D. et al. Development and pharmacological characterization of a rat model of osteoarthritis pain. Pain 114, 339\u2013346 https:\/\/doi.org\/10.1016\/j.pain.2004.11.008 (2005).","journal-title":"Pain"},{"key":"1926_CR65","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1080\/27697061.2023.2209880","volume":"43","author":"SB Kwon","year":"2024","unstructured":"Kwon, S. B. et al. A blend of Tamarindus Indica and Curcuma Longa extracts Alleviates Monosodium Iodoacetate (MIA)-induced osteoarthritic pain and joint inflammation in rats. J. Am. Nutr. Assoc. 43, 48\u201358 https:\/\/doi.org\/10.1080\/27697061.2023.2209880 (2024).","journal-title":"J. Am. Nutr. Assoc."},{"key":"1926_CR66","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1007\/s10787-022-01060-5","volume":"30","author":"YS Lee","year":"2022","unstructured":"Lee, Y. S., Kim, S. M., Park, E. J. & Lee, H. J. Anti-arthritic effects of Schisandra chinensis extract in monosodium iodoacetate-induced osteoarthritis rats. Inflammopharmacology 30, 2261\u20132272 https:\/\/doi.org\/10.1007\/s10787-022-01060-5 (2022).","journal-title":"Inflammopharmacology"},{"key":"1926_CR67","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1097\/j.pain.0000000000001466","volume":"160","author":"Y Sakurai","year":"2019","unstructured":"Sakurai, Y. et al. Contribution of synovial macrophages to rat advanced osteoarthritis pain resistant to cyclooxygenase inhibitors. Pain 160, 895\u2013907 https:\/\/doi.org\/10.1097\/j.pain.0000000000001466 (2019).","journal-title":"Pain"},{"key":"1926_CR68","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jep.2010.07.025","volume":"131","author":"M Kang","year":"2010","unstructured":"Kang, M. et al. The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo. J. Ethnopharmacol. 131, 485\u2013496 https:\/\/doi.org\/10.1016\/j.jep.2010.07.025 (2010).","journal-title":"J. Ethnopharmacol."},{"key":"1926_CR69","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s13018-018-0967-y","volume":"13","author":"YJ Chou","year":"2018","unstructured":"Chou, Y. J. et al. The potent anti-inflammatory effect of Guilu Erxian Glue extracts remedy joint pain and ameliorate the progression of osteoarthritis in mice. J. Orthop. Surg. Res. 13, 259 https:\/\/doi.org\/10.1186\/s13018-018-0967-y (2018).","journal-title":"J. Orthop. Surg. Res."},{"key":"1926_CR70","doi-asserted-by":"publisher","unstructured":"Park, H. S., Park, E. J. & Lee, H. J. Curcuminoids phospholipid attenuates osteoarthritis and protects cartilage in a monosodium iodoacetate-induced rat model. Nutrients 18 https:\/\/doi.org\/10.3390\/nu18071111 (2026).","DOI":"10.3390\/nu18071111"},{"key":"1926_CR71","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1016\/j.joca.2015.05.001","volume":"23","author":"LA Bryden","year":"2015","unstructured":"Bryden, L. A., Nicholson, J. R., Doods, H. & Pekcec, A. Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy. Osteoarthr. Cartil. 23, 1605\u20131612 https:\/\/doi.org\/10.1016\/j.joca.2015.05.001 (2015).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR72","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.pain.2006.12.022","volume":"128","author":"SP Ivanavicius","year":"2007","unstructured":"Ivanavicius, S. P. et al. Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain 128, 272\u2013282 https:\/\/doi.org\/10.1016\/j.pain.2006.12.022 (2007).","journal-title":"Pain"},{"key":"1926_CR73","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2025.117542","volume":"198","author":"N Ruggiero","year":"2025","unstructured":"Ruggiero, N. et al. The effect of celecoxib and muMab911 on strain adaptive bone remodeling and fracture repair in female mice: implications for rapidly progressive osteoarthritis. Bone 198, 117542 https:\/\/doi.org\/10.1016\/j.bone.2025.117542 (2025).","journal-title":"Bone"},{"key":"1926_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.134990","volume":"729","author":"S Yoneda","year":"2020","unstructured":"Yoneda, S. et al. Duloxetine ameliorates the impairment of diffuse noxious inhibitory control in rat models of peripheral neuropathic pain and knee osteoarthritis pain. Neurosci. Lett. 729, 134990 https:\/\/doi.org\/10.1016\/j.neulet.2020.134990 (2020).","journal-title":"Neurosci. Lett."},{"key":"1926_CR75","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13075-020-2096-3","volume":"22","author":"HT Philpott","year":"2020","unstructured":"Philpott, H. T. & McDougall, J. J. Combatting joint pain and inflammation by dual inhibition of monoacylglycerol lipase and cyclooxygenase-2 in a rat model of osteoarthritis. Arthritis Res. Ther. 22, 9 https:\/\/doi.org\/10.1186\/s13075-020-2096-3 (2020).","journal-title":"Arthritis Res. Ther."},{"key":"1926_CR76","doi-asserted-by":"publisher","unstructured":"Yu, M. et al. Salmon nasal cartilage proteoglycan ameliorate joint pain and cartilage degradation by regulating catabolic and anabolic homeostasis in MIA-induced osteoarthritis. Nutrients 18 https:\/\/doi.org\/10.3390\/nu18010176 (2026).","DOI":"10.3390\/nu18010176"},{"key":"1926_CR77","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/ejp.1478","volume":"24","author":"ZH Wen","year":"2020","unstructured":"Wen, Z. H. et al. The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: the roles of TGF-beta1 and NGF expressions in chondrocytes. Eur. J. Pain. 24, 209\u2013222 https:\/\/doi.org\/10.1002\/ejp.1478 (2020).","journal-title":"Eur. J. Pain."},{"key":"1926_CR78","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.70068","volume":"29","author":"CS Sung","year":"2025","unstructured":"Sung, C. S. et al. Varying analgesic effectiveness of systemic and central intrathecal administration of cyclooxygenase-2 inhibitors in different phases of osteoarthritic pain in rats. Eur. J. Pain. 29, e70068 https:\/\/doi.org\/10.1002\/ejp.70068 (2025).","journal-title":"Eur. J. Pain."},{"key":"1926_CR79","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.biopha.2016.06.050","volume":"83","author":"ZM Wang","year":"2016","unstructured":"Wang, Z. M., Chen, Y. C. & Wang, D. P. Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats. Biomed. Pharmacother. 83, 763\u2013770 https:\/\/doi.org\/10.1016\/j.biopha.2016.06.050 (2016).","journal-title":"Biomed. Pharmacother."},{"key":"1926_CR80","doi-asserted-by":"publisher","first-page":"454","DOI":"10.4103\/0971-5916.159296","volume":"141","author":"RR Kumari","year":"2015","unstructured":"Kumari, R. R. et al. Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats. Indian J. Med. Res. 141, 454\u2013462 https:\/\/doi.org\/10.4103\/0971-5916.159296 (2015).","journal-title":"Indian J. Med. Res."},{"key":"1926_CR81","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.pbb.2012.12.013","volume":"103","author":"AS More","year":"2013","unstructured":"More, A. S. et al. Effect of iNOS inhibitor S-methylisothiourea in monosodium iodoacetate-induced osteoathritic pain: implication for osteoarthritis therapy. Pharm. Biochem. Behav. 103, 764\u2013772 https:\/\/doi.org\/10.1016\/j.pbb.2012.12.013 (2013).","journal-title":"Pharm. Biochem. Behav."},{"key":"1926_CR82","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1080\/03007995.2017.1417245","volume":"34","author":"K Reed","year":"2018","unstructured":"Reed, K., Collaku, A. & Moreira, S. Efficacy and safety of twice daily sustained-release paracetamol formulation for osteoarthritis pain of the knee or hip: a randomized, double-blind, placebo-controlled, twelve-week study. Curr. Med. Res. Opin. 34, 689\u2013699 https:\/\/doi.org\/10.1080\/03007995.2017.1417245 (2018).","journal-title":"Curr. Med. Res. Opin."},{"key":"1926_CR83","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s40122-019-0125-1","volume":"8","author":"AJ Kivitz","year":"2019","unstructured":"Kivitz, A. J., Conaghan, P. G., Cinar, A., Lufkin, J. & Kelley, S. D. Rescue analgesic medication use by patients treated with triamcinolone acetonide extended-release for knee osteoarthritis pain: pooled analysis of three phase 2\/3 randomized clinical trials. Pain. Ther. 8, 271\u2013280 https:\/\/doi.org\/10.1007\/s40122-019-0125-1 (2019).","journal-title":"Pain. Ther."},{"key":"1926_CR84","doi-asserted-by":"publisher","first-page":"1134S","DOI":"10.1177\/19476035211046042","volume":"13","author":"C Caglar","year":"2021","unstructured":"Caglar, C., Kara, H., Ates, O. & Ugurlu, M. Evaluation of different intraarticular injection therapies with gait analysis in a rat osteoarthritis model. Cartilage 13, 1134S\u20131143S https:\/\/doi.org\/10.1177\/19476035211046042 (2021).","journal-title":"Cartilage"},{"key":"1926_CR85","doi-asserted-by":"publisher","unstructured":"Tschon, M. et al. Boosting the intra-articular efficacy of low dose corticosteroid through a biopolymeric matrix: an in vivo model of osteoarthritis. Cells 9 https:\/\/doi.org\/10.3390\/cells9071571 (2020).","DOI":"10.3390\/cells9071571"},{"key":"1926_CR86","doi-asserted-by":"publisher","unstructured":"Micheli, L. et al. Intra-articular route for the system of molecules 14G1862 from Centella asiatica: pain relieving and protective effects in a rat model of osteoarthritis. Nutrients 12 https:\/\/doi.org\/10.3390\/nu12061618 (2020).","DOI":"10.3390\/nu12061618"},{"key":"1926_CR87","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2905104","volume":"2017","author":"V Chapman","year":"2017","unstructured":"Chapman, V. et al. Therapeutic benefit for late, but not early, passage mesenchymal stem cells on pain behaviour in an animal model of osteoarthritis. Stem Cells Int. 2017, 2905104 https:\/\/doi.org\/10.1155\/2017\/2905104 (2017).","journal-title":"Stem Cells Int."},{"key":"1926_CR88","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.joca.2013.06.031","volume":"21","author":"PI Mapp","year":"2013","unstructured":"Mapp, P. I. et al. Differences in structural and pain phenotypes in the sodium monoiodoacetate and meniscal transection models of osteoarthritis. Osteoarthr. Cartil. 21, 1336\u20131345 https:\/\/doi.org\/10.1016\/j.joca.2013.06.031 (2013).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR89","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1007\/s10067-018-4087-1","volume":"37","author":"HS Pawar","year":"2018","unstructured":"Pawar, H. S., Francis, N. K., Hota, T., Peter, N. & Mitra, A. Comparative evaluation of therapeutic efficacy of intra-articular oxaceprol with conventional modalities in osteoarthritis animal model. Clin. Rheumatol. 37, 2195\u20132201 https:\/\/doi.org\/10.1007\/s10067-018-4087-1 (2018).","journal-title":"Clin. Rheumatol."},{"key":"1926_CR90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2016.06.049","volume":"591","author":"JS Kroin","year":"2016","unstructured":"Kroin, J. S. et al. Intraarticular slow-release triamcinolone acetate reduces allodynia in an experimental mouse knee osteoarthritis model. Gene 591, 1\u20135 https:\/\/doi.org\/10.1016\/j.gene.2016.06.049 (2016).","journal-title":"Gene"},{"key":"1926_CR91","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.jpainsymman.2006.11.017","volume":"34","author":"F Burch","year":"2007","unstructured":"Burch, F. et al. A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis. J. Pain. Symptom Manag 34, 328\u2013338 https:\/\/doi.org\/10.1016\/j.jpainsymman.2006.11.017 (2007).","journal-title":"J. Pain. Symptom Manag"},{"key":"1926_CR92","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neulet.2004.08.023","volume":"370","author":"R Combe","year":"2004","unstructured":"Combe, R., Bramwell, S. & Field, M. J. The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats?. Neurosci. Lett. 370, 236\u2013240 https:\/\/doi.org\/10.1016\/j.neulet.2004.08.023 (2004).","journal-title":"Neurosci. Lett."},{"key":"1926_CR93","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/jor.25208","volume":"40","author":"K Kanno","year":"2022","unstructured":"Kanno, K. et al. Analgesic effects and arthritic changes following tramadol administration in a rat hip osteoarthritis model. J. Orthop. Res. 40, 1770\u20131777 https:\/\/doi.org\/10.1002\/jor.25208 (2022).","journal-title":"J. Orthop. Res."},{"key":"1926_CR94","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.pain.2011.09.007","volume":"153","author":"CB Knights","year":"2012","unstructured":"Knights, C. B., Gentry, C. & Bevan, S. Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL\/6 mice. Pain 153, 281\u2013292 https:\/\/doi.org\/10.1016\/j.pain.2011.09.007 (2012).","journal-title":"Pain"},{"key":"1926_CR95","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2147\/JPR.S30540","volume":"5","author":"I Steigerwald","year":"2012","unstructured":"Steigerwald, I., Muller, M., Kujawa, J., Balblanc, J. C. & Calvo-Alen, J. Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-label, phase 3b study. J. Pain Res. 5, 121\u2013138 https:\/\/doi.org\/10.2147\/JPR.S30540 (2012).","journal-title":"J. Pain Res."},{"key":"1926_CR96","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1517\/14656566.2010.497720","volume":"11","author":"R Buynak","year":"2010","unstructured":"Buynak, R. et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. Expert Opin. Pharmacother. 11, 1787\u20131804 https:\/\/doi.org\/10.1517\/14656566.2010.497720 (2010).","journal-title":"Expert Opin. Pharmacother."},{"key":"1926_CR97","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1016\/j.clinthera.2015.08.014","volume":"37","author":"R Buynak","year":"2015","unstructured":"Buynak, R. et al. Long-term safety and efficacy of tapentadol extended release following up to 2 years of treatment in patients with moderate to severe, chronic pain: results of an open-label extension trial. Clin. Ther. 37, 2420\u20132438 https:\/\/doi.org\/10.1016\/j.clinthera.2015.08.014 (2015).","journal-title":"Clin. Ther."},{"key":"1926_CR98","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1007\/s12325-014-0128-6","volume":"31","author":"M Etropolski","year":"2014","unstructured":"Etropolski, M. et al. Safety and tolerability of tapentadol extended release in moderate to severe chronic osteoarthritis or low back pain management: pooled analysis of randomized controlled trials. Adv. Ther. 31, 604\u2013620 https:\/\/doi.org\/10.1007\/s12325-014-0128-6 (2014).","journal-title":"Adv. Ther."},{"key":"1926_CR99","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1080\/08982104.2020.1730400","volume":"31","author":"M Bishnoi","year":"2021","unstructured":"Bishnoi, M., Jain, A., Singla, Y. & Shrivastava, B. Sublingual delivery of chondroitin sulfate conjugated tapentadol loaded nanovesicles for the treatment of osteoarthritis. J. Liposome Res. 31, 30\u201344 https:\/\/doi.org\/10.1080\/08982104.2020.1730400 (2021).","journal-title":"J. Liposome Res."},{"key":"1926_CR100","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2147\/JPR.S120170","volume":"10","author":"M Hale","year":"2017","unstructured":"Hale, M., Urdaneta, V., Kirby, M. T., Xiang, Q. & Rauck, R. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids. J. Pain Res. 10, 233\u2013240 https:\/\/doi.org\/10.2147\/JPR.S120170 (2017).","journal-title":"J. Pain Res."},{"key":"1926_CR101","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.joca.2012.08.006","volume":"20","author":"SC Fu","year":"2012","unstructured":"Fu, S. C., Cheuk, Y. C., Hung, L. K. & Chan, K. M. Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis. Osteoarthr. Cartil. 20, 1409\u20131416 https:\/\/doi.org\/10.1016\/j.joca.2012.08.006 (2012).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR102","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41584-020-00523-9","volume":"17","author":"NK Arden","year":"2021","unstructured":"Arden, N. K. et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat. Rev. Rheumatol. 17, 59\u201366 https:\/\/doi.org\/10.1038\/s41584-020-00523-9 (2021).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1926_CR103","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.3950\/jibiinkoka.93.1064","volume":"93","author":"T Haneda","year":"1990","unstructured":"Haneda, T. [Clinico-experimental study on parapharyngeal space invasion of head and neck cancer]. Nihon Jibiinkoka Gakkai Kaiho 93, 1064\u20131075 https:\/\/doi.org\/10.3950\/jibiinkoka.93.1064 (1990).","journal-title":"Nihon Jibiinkoka Gakkai Kaiho"},{"key":"1926_CR104","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1185\/03007995.2011.633502","volume":"27","author":"EP Frakes","year":"2011","unstructured":"Frakes, E. P., Risser, R. C., Ball, T. D., Hochberg, M. C. & Wohlreich, M. M. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr. Med. Res. Opin. 27, 2361\u20132372 https:\/\/doi.org\/10.1185\/03007995.2011.633502 (2011).","journal-title":"Curr. Med. Res. Opin."},{"key":"1926_CR105","doi-asserted-by":"publisher","first-page":"809","DOI":"10.2147\/JPR.S164128","volume":"11","author":"Y Uchio","year":"2018","unstructured":"Uchio, Y. et al. A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. J. Pain Res. 11, 809\u2013821 https:\/\/doi.org\/10.2147\/JPR.S164128 (2018).","journal-title":"J. Pain Res."},{"key":"1926_CR106","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2147\/OARRR.S193044","volume":"11","author":"L Yue","year":"2019","unstructured":"Yue, L. et al. Clinical meaningfulness of duloxetine\u2019s effect in Chinese patients with chronic pain due to osteoarthritis: post hoc analyses of a phase 3 randomized trial. Open Access Rheumatol. 11, 67\u201376 https:\/\/doi.org\/10.2147\/OARRR.S193044 (2019).","journal-title":"Open Access Rheumatol."},{"key":"1926_CR107","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1002\/jor.24480","volume":"38","author":"Y Kawarai","year":"2020","unstructured":"Kawarai, Y. et al. Analgesic effect of duloxetine on an animal model of monosodium iodoacetate-induced hip osteoarthritis. J. Orthop. Res. 38, 422\u2013430 https:\/\/doi.org\/10.1002\/jor.24480 (2020).","journal-title":"J. Orthop. Res."},{"key":"1926_CR108","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115360","volume":"166","author":"K Nastic","year":"2023","unstructured":"Nastic, K. et al. The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis. Biomed. Pharmacother. 166, 115360 https:\/\/doi.org\/10.1016\/j.biopha.2023.115360 (2023).","journal-title":"Biomed. Pharmacother."},{"key":"1926_CR109","doi-asserted-by":"publisher","DOI":"10.1186\/ar2121","volume":"9","author":"B Beyreuther","year":"2007","unstructured":"Beyreuther, B., Callizot, N. & Stohr, T. Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain. Arthritis Res. Ther. 9, R14 https:\/\/doi.org\/10.1186\/ar2121 (2007).","journal-title":"Arthritis Res. Ther."},{"key":"1926_CR110","doi-asserted-by":"publisher","first-page":"3695","DOI":"10.1002\/ptr.8223","volume":"38","author":"G Tshering","year":"2024","unstructured":"Tshering, G., Posadzki, P. & Kongkaew, C. Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: a systematic review and meta-analysis. Phytother. Res. 38, 3695\u20133705 https:\/\/doi.org\/10.1002\/ptr.8223 (2024).","journal-title":"Phytother. Res."},{"key":"1926_CR111","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.ejphar.2010.05.022","volume":"641","author":"KM Kalff","year":"2010","unstructured":"Kalff, K. M. et al. Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate. Eur. J. Pharm. 641, 108\u2013113 https:\/\/doi.org\/10.1016\/j.ejphar.2010.05.022 (2010).","journal-title":"Eur. J. Pharm."},{"key":"1926_CR112","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25581-8","volume":"8","author":"AR Haywood","year":"2018","unstructured":"Haywood, A. R., Hathway, G. J. & Chapman, V. Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis. Sci. Rep. 8, 7122 https:\/\/doi.org\/10.1038\/s41598-018-25581-8 (2018).","journal-title":"Sci. Rep."},{"key":"1926_CR113","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X221080377","volume":"14","author":"F Meng","year":"2022","unstructured":"Meng, F. et al. Efficacy and safety of biologic agents for the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Ther. Adv. Musculoskelet. Dis. 14, 1759720X221080377 https:\/\/doi.org\/10.1177\/1759720X221080377 (2022).","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"1926_CR114","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-025-08402-8","volume":"26","author":"SJ DiMartino","year":"2025","unstructured":"DiMartino, S. J. et al. Efficacy and safety of fasinumab in an NSAID-controlled study in patients with pain due to osteoarthritis of the knee or hip. BMC Musculoskelet. Disord. 26, 192 https:\/\/doi.org\/10.1186\/s12891-025-08402-8 (2025).","journal-title":"BMC Musculoskelet. Disord."},{"key":"1926_CR115","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1002\/art.41012","volume":"71","author":"P Dakin","year":"2019","unstructured":"Dakin, P. et al. The efficacy, tolerability, and joint safety of Fasinumab in osteoarthritis pain: a phase IIb\/III double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheumatol. 71, 1824\u20131834 https:\/\/doi.org\/10.1002\/art.41012 (2019).","journal-title":"Arthritis Rheumatol."},{"key":"1926_CR116","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2024.100533","volume":"6","author":"SJ DiMartino","year":"2024","unstructured":"DiMartino, S. J. et al. A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip. Osteoarthr. Cartil. Open 6, 100533 https:\/\/doi.org\/10.1016\/j.ocarto.2024.100533 (2024).","journal-title":"Osteoarthr. Cartil. Open"},{"key":"1926_CR117","doi-asserted-by":"publisher","unstructured":"DiMartino, S. J. et al. A phase III, randomised, double-blind, multi-dose, placebo- and naproxen-controlled study to evaluate the efficacy and safety of fasinumab in patients with pain due to osteoarthritis of the knee or hip. RMD Open 12 https:\/\/doi.org\/10.1136\/rmdopen-2025-006436 (2026).","DOI":"10.1136\/rmdopen-2025-006436"},{"key":"1926_CR118","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.pain.2013.04.035","volume":"154","author":"ELH Spierings","year":"2013","unstructured":"Spierings, E. L. H. et al. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee. Pain 154, 1603\u20131612 https:\/\/doi.org\/10.1016\/j.pain.2013.04.035 (2013).","journal-title":"Pain"},{"key":"1926_CR119","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.3899\/jrheum.131294","volume":"41","author":"EF Ekman","year":"2014","unstructured":"Ekman, E. F. et al. Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen. J. Rheumatol. 41, 2249\u20132259 https:\/\/doi.org\/10.3899\/jrheum.131294 (2014).","journal-title":"J. Rheumatol."},{"key":"1926_CR120","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/art.37950","volume":"65","author":"MT Brown","year":"2013","unstructured":"Brown, M. T. et al. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial. Arthritis Rheum. 65, 1795\u20131803 https:\/\/doi.org\/10.1002\/art.37950 (2013).","journal-title":"Arthritis Rheum."},{"key":"1926_CR121","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.jpain.2012.05.006","volume":"13","author":"MT Brown","year":"2012","unstructured":"Brown, M. T. et al. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J. Pain. 13, 790\u2013798 https:\/\/doi.org\/10.1016\/j.jpain.2012.05.006 (2012).","journal-title":"J. Pain."},{"key":"1926_CR122","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s13075-022-02759-0","volume":"24","author":"T Neogi","year":"2022","unstructured":"Neogi, T. et al. Observed efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized NSAID-controlled study. Arthritis Res. Ther. 24, 78 https:\/\/doi.org\/10.1186\/s13075-022-02759-0 (2022).","journal-title":"Arthritis Res. Ther."},{"key":"1926_CR123","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1136\/annrheumdis-2013-204905","volume":"74","author":"TJ Schnitzer","year":"2015","unstructured":"Schnitzer, T. J. et al. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann. Rheum. Dis. 74, 1202\u20131211 https:\/\/doi.org\/10.1136\/annrheumdis-2013-204905 (2015).","journal-title":"Ann. Rheum. Dis."},{"key":"1926_CR124","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.joca.2011.09.006","volume":"19","author":"H Nagashima","year":"2011","unstructured":"Nagashima, H. et al. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthr. Cartil. 19, 1405\u20131412 https:\/\/doi.org\/10.1016\/j.joca.2011.09.006 (2011).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR125","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1136\/annrheumdis-2019-216296","volume":"79","author":"F Berenbaum","year":"2020","unstructured":"Berenbaum, F. et al. Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period. Ann. Rheum. Dis. 79, 800\u2013810 https:\/\/doi.org\/10.1136\/annrheumdis-2019-216296 (2020).","journal-title":"Ann. Rheum. Dis."},{"key":"1926_CR126","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.joca.2011.01.009","volume":"19","author":"TJ Schnitzer","year":"2011","unstructured":"Schnitzer, T. J. et al. Long-term open-label study of tanezumab for moderate to severe osteoarthritic knee pain. Osteoarthr. Cartil. 19, 639\u2013646 https:\/\/doi.org\/10.1016\/j.joca.2011.01.009 (2011).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR127","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1016\/j.joca.2016.05.015","volume":"24","author":"L Xu","year":"2016","unstructured":"Xu, L. et al. The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain. Osteoarthr. Cartil. 24, 1587\u20131595 https:\/\/doi.org\/10.1016\/j.joca.2016.05.015 (2016).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR128","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1792-x","volume":"18","author":"M Miyagi","year":"2017","unstructured":"Miyagi, M. et al. Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice. BMC Musculoskelet. Disord. 18, 428 https:\/\/doi.org\/10.1186\/s12891-017-1792-x (2017).","journal-title":"BMC Musculoskelet. Disord."},{"key":"1926_CR129","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1136\/annrheumdis-2015-208913","volume":"76","author":"TP LaBranche","year":"2017","unstructured":"LaBranche, T. P. et al. Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model. Ann. Rheum. Dis. 76, 295\u2013302 https:\/\/doi.org\/10.1136\/annrheumdis-2015-208913 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"1926_CR130","doi-asserted-by":"publisher","unstructured":"Tian, Y. et al. Local administration of low-dose nerve growth factor antibody reduced pain in a rat osteoarthritis model. Int. J. Mol. Sci. 22 https:\/\/doi.org\/10.3390\/ijms22052552 (2021).","DOI":"10.3390\/ijms22052552"},{"key":"1926_CR131","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.joca.2015.02.002","volume":"23","author":"G Ishikawa","year":"2015","unstructured":"Ishikawa, G., Koya, Y., Tanaka, H. & Nagakura, Y. Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis. Osteoarthr. Cartil. 23, 925\u2013932 https:\/\/doi.org\/10.1016\/j.joca.2015.02.002 (2015).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR132","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1136\/annrheumdis-2018-214489","volume":"78","author":"IS von Loga","year":"2019","unstructured":"von Loga, I. S. et al. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Ann. Rheum. Dis. 78, 672\u2013675 https:\/\/doi.org\/10.1136\/annrheumdis-2018-214489 (2019).","journal-title":"Ann. Rheum. Dis."},{"key":"1926_CR133","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynpai.2023.100136","volume":"14","author":"S Somersan-Karakaya","year":"2023","unstructured":"Somersan-Karakaya, S. et al. Monoclonal antibodies against GFRalpha3 are efficacious against evoked hyperalgesic and allodynic responses in mouse join pain models but, one of these, REGN5069, was not effective against pain in a randomized, placebo-controlled clinical trial in patients with osteoarthritis pain. Neurobiol. Pain. 14, 100136 https:\/\/doi.org\/10.1016\/j.ynpai.2023.100136 (2023).","journal-title":"Neurobiol. Pain."},{"key":"1926_CR134","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1016\/j.joca.2018.08.019","volume":"26","author":"Y Jin","year":"2018","unstructured":"Jin, Y. et al. CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial. Osteoarthr. Cartil. 26, 1609\u20131618 https:\/\/doi.org\/10.1016\/j.joca.2018.08.019 (2018).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR135","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.joca.2014.01.009","volume":"22","author":"RJ Benschop","year":"2014","unstructured":"Benschop, R. J. et al. Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain. Osteoarthr. Cartil. 22, 578\u2013585 https:\/\/doi.org\/10.1016\/j.joca.2014.01.009 (2014).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR136","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/nm.4324","volume":"23","author":"OH Jeon","year":"2017","unstructured":"Jeon, O. H. et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat. Med. 23, 775\u2013781 https:\/\/doi.org\/10.1038\/nm.4324 (2017).","journal-title":"Nat. Med."},{"key":"1926_CR137","doi-asserted-by":"publisher","first-page":"854","DOI":"10.55563\/clinexprheumatol\/hjt118","volume":"43","author":"Y Yazici","year":"2025","unstructured":"Yazici, Y. et al. A Phase 3, 56-week, randomised, double-blind, placebo-controlled study (OA-11) utilising patient-reported and radiographic outcomes evaluating the efficacy and safety of a lorecivivint injection in patients with moderate to severe knee osteoarthritis. Clin. Exp. Rheumatol. 43, 854\u2013860 https:\/\/doi.org\/10.55563\/clinexprheumatol\/hjt118 (2025).","journal-title":"Clin. Exp. Rheumatol."},{"key":"1926_CR138","doi-asserted-by":"publisher","first-page":"847","DOI":"10.55563\/clinexprheumatol\/gskbin","volume":"43","author":"Y Yazici","year":"2025","unstructured":"Yazici, Y. et al. A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients. Clin. Exp. Rheumatol. 43, 847\u2013853 https:\/\/doi.org\/10.55563\/clinexprheumatol\/gskbin (2025).","journal-title":"Clin. Exp. Rheumatol."},{"key":"1926_CR139","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.joca.2021.02.004","volume":"29","author":"Y Yazici","year":"2021","unstructured":"Yazici, Y. et al. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2\/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthr. Cartil. 29, 654\u2013666 https:\/\/doi.org\/10.1016\/j.joca.2021.02.004 (2021).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR140","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1002\/art.41315","volume":"72","author":"Y Yazici","year":"2020","unstructured":"Yazici, Y. et al. Lorecivivint, a novel intraarticular CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1A inhibitor and Wnt pathway modulator for the treatment of knee osteoarthritis: a phase II randomized trial. Arthritis Rheumatol. 72, 1694\u20131706 https:\/\/doi.org\/10.1002\/art.41315 (2020).","journal-title":"Arthritis Rheumatol."},{"key":"1926_CR141","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s40744-024-00731-9","volume":"12","author":"CJ Swearingen","year":"2025","unstructured":"Swearingen, C. J. et al. Evaluation of safety and efficacy of a single lorecivivint injection in patients with knee osteoarthritis: a multicenter, observational extension trial. Rheumatol. Ther. 12, 157\u2013171 https:\/\/doi.org\/10.1007\/s40744-024-00731-9 (2025).","journal-title":"Rheumatol. Ther."},{"key":"1926_CR142","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.joca.2019.05.006","volume":"27","author":"V Deshmukh","year":"2019","unstructured":"Deshmukh, V. et al. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthr. Cartil. 27, 1347\u20131360 https:\/\/doi.org\/10.1016\/j.joca.2019.05.006 (2019).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR143","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1124\/jpet.109.159657","volume":"331","author":"C Cialdai","year":"2009","unstructured":"Cialdai, C., Giuliani, S., Valenti, C., Tramontana, M. & Maggi, C. A. Effect of Intra-articular 4-(S)-amino-5-(4-4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132), a kinin B2 receptor antagonist, on nociceptive response in monosodium iodoacetate-induced experimental osteoarthritis in rats. J. Pharm. Exp. Ther. 331, 1025\u20131032 https:\/\/doi.org\/10.1124\/jpet.109.159657 (2009).","journal-title":"J. Pharm. Exp. Ther."},{"key":"1926_CR144","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/j.joca.2013.06.017","volume":"21","author":"JR Matyas","year":"2013","unstructured":"Matyas, J. R., Gutmann, A., Randev, J., Hurtig, M. & Bertram, J. E. Intra-articular anaesthesia mitigates established pain in experimental osteoarthritis: a preliminary study of gait impulse redistribution as a biomarker of analgesia pharmacodynamics. Osteoarthr. Cartil. 21, 1365\u20131373 https:\/\/doi.org\/10.1016\/j.joca.2013.06.017 (2013).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR145","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/1471-2296-14-195","volume":"14","author":"Z Paskins","year":"2013","unstructured":"Paskins, Z., Sanders, T. & Hassell, A. B. What influences patients with osteoarthritis to consult their GP about their symptoms? A narrative review. BMC Fam. Pr. 14, 195 https:\/\/doi.org\/10.1186\/1471-2296-14-195 (2013).","journal-title":"BMC Fam. Pr."},{"key":"1926_CR146","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nrn2606-c1","volume":"10","author":"AD Craig","year":"2009","unstructured":"Craig, A. D. A rat is not a monkey is not a human: comment on Mogil (Nature Rev. Neurosci. 10, 283-294 (2009)). Nat. Rev. Neurosci. 10, 466 https:\/\/doi.org\/10.1038\/nrn2606-c1 (2009).","journal-title":"Nat. Rev. Neurosci."},{"key":"1926_CR147","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1097\/j.pain.0000000000001973","volume":"161","author":"S Shiers","year":"2020","unstructured":"Shiers, S., Klein, R. M. & Price, T. J. Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization. Pain 161, 2410\u20132424 https:\/\/doi.org\/10.1097\/j.pain.0000000000001973 (2020).","journal-title":"Pain"},{"key":"1926_CR148","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1097\/j.pain.0000000000003697","volume":"166","author":"MA Huerta","year":"2025","unstructured":"Huerta, M. A., Roza, P., Cisneros, E., Alique, M. & Roza, C. Enhancing clinical translation of analgesics for neuropathic pain: a systematic review and meta-analysis on the role of non-evoked pain assessment in preclinical trials. Pain 166, 2473\u20132486 https:\/\/doi.org\/10.1097\/j.pain.0000000000003697 (2025).","journal-title":"Pain"},{"key":"1926_CR149","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/s41583-021-00536-7","volume":"23","author":"KE Sadler","year":"2022","unstructured":"Sadler, K. E., Mogil, J. S. & Stucky, C. L. Innovations and advances in modelling and measuring pain in animals. Nat. Rev. Neurosci. 23, 70\u201385 https:\/\/doi.org\/10.1038\/s41583-021-00536-7 (2022).","journal-title":"Nat. Rev. Neurosci."},{"key":"1926_CR150","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41592-018-0224-7","volume":"15","author":"AH Tuttle","year":"2018","unstructured":"Tuttle, A. H., Philip, V. M., Chesler, E. J. & Mogil, J. S. Comparing phenotypic variation between inbred and outbred mice. Nat. Methods 15, 994\u2013996 https:\/\/doi.org\/10.1038\/s41592-018-0224-7 (2018).","journal-title":"Nat. Methods"},{"key":"1926_CR151","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.603186","volume":"12","author":"C Cho","year":"2021","unstructured":"Cho, C., Deol, H. K. & Martin, L. J. Bridging the translational divide in pain research: biological, psychological and social considerations. Front. Pharm. 12, 603186 https:\/\/doi.org\/10.3389\/fphar.2021.603186 (2021).","journal-title":"Front. Pharm."},{"key":"1926_CR152","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77640-8","volume":"10","author":"S Hestehave","year":"2020","unstructured":"Hestehave, S. et al. The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury. Sci. Rep. 10, 20981 https:\/\/doi.org\/10.1038\/s41598-020-77640-8 (2020).","journal-title":"Sci. Rep."},{"key":"1926_CR153","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105749","volume":"163","author":"JS Mogil","year":"2024","unstructured":"Mogil, J. S., Parisien, M., Esfahani, S. J. & Diatchenko, L. Sex differences in mechanisms of pain hypersensitivity. Neurosci. Biobehav. Rev. 163, 105749 https:\/\/doi.org\/10.1016\/j.neubiorev.2024.105749 (2024).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1926_CR154","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.jconrel.2012.01.020","volume":"161","author":"Y Perrie","year":"2012","unstructured":"Perrie, Y. et al. The impact of ageing on the barriers to drug delivery. J. Control Release 161, 389\u2013398 https:\/\/doi.org\/10.1016\/j.jconrel.2012.01.020 (2012).","journal-title":"J. Control Release"},{"key":"1926_CR155","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/s41430-018-0324-6","volume":"73","author":"LE Pappas","year":"2019","unstructured":"Pappas, L. E. & Nagy, T. R. The translation of age-related body composition findings from rodents to humans. Eur. J. Clin. Nutr. 73, 172\u2013178 https:\/\/doi.org\/10.1038\/s41430-018-0324-6 (2019).","journal-title":"Eur. J. Clin. Nutr."},{"key":"1926_CR156","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1636","volume":"10","author":"SK Akula","year":"2020","unstructured":"Akula, S. K., McCullough, K. B., Weichselbaum, C., Dougherty, J. D. & Maloney, S. E. The trajectory of gait development in mice. Brain Behav. 10, e01636 https:\/\/doi.org\/10.1002\/brb3.1636 (2020).","journal-title":"Brain Behav."},{"key":"1926_CR157","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-9-95","volume":"9","author":"GM van Dijk","year":"2008","unstructured":"van Dijk, G. M. et al. Comorbidity, limitations in activities and pain in patients with osteoarthritis of the hip or knee. BMC Musculoskelet. Disord. 9, 95 https:\/\/doi.org\/10.1186\/1471-2474-9-95 (2008).","journal-title":"BMC Musculoskelet. Disord."},{"key":"1926_CR158","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.jconrel.2022.06.015","volume":"348","author":"T Siefen","year":"2022","unstructured":"Siefen, T., Bjerregaard, S., Borglin, C. & Lamprecht, A. Assessment of joint pharmacokinetics and consequences for the intraarticular delivery of biologics. J. Control Release 348, 745\u2013759 https:\/\/doi.org\/10.1016\/j.jconrel.2022.06.015 (2022).","journal-title":"J. Control Release"},{"key":"1926_CR159","first-page":"53","volume":"35","author":"D Cimino Brown","year":"2017","unstructured":"Cimino Brown, D. What can we learn from osteoarthritis pain in companion animals?. Clin. Exp. Rheumatol. 35, 53\u201358 (2017).","journal-title":"Clin. Exp. Rheumatol."},{"key":"1926_CR160","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.joca.2017.11.011","volume":"26","author":"BDX Lascelles","year":"2018","unstructured":"Lascelles, B. D. X., Brown, D. C., Maixner, W. & Mogil, J. S. Spontaneous painful disease in companion animals can facilitate the development of chronic pain therapies for humans. Osteoarthr. Cartil. 26, 175\u2013183 https:\/\/doi.org\/10.1016\/j.joca.2017.11.011 (2018).","journal-title":"Osteoarthr. Cartil."},{"key":"1926_CR161","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2174\/1871523017666180126150341","volume":"16","author":"S Murugan","year":"2017","unstructured":"Murugan, S., Bethapudi, B., Purusothaman, D., Chandrasekaran, P. R. & Velusami, C. C. Antiarthritic effect of polar extract of Curcuma longa on monosodium iodoacetate induced osteoarthritis in rats. Antiinflamm Antiallergy Agents Med. Chem. 16, 193\u2013202 https:\/\/doi.org\/10.2174\/1871523017666180126150341 (2017).","journal-title":"Antiinflamm Antiallergy Agents Med. Chem."},{"key":"1926_CR162","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.2147\/JPR.S171395","volume":"11","author":"Y Uchio","year":"2018","unstructured":"Uchio, Y. et al. Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study. J. Pain Res. 11, 1391\u20131403 https:\/\/doi.org\/10.2147\/JPR.S171395 (2018).","journal-title":"J. Pain Res."}],"container-title":["Communications Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01926-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01926-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01926-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:13:18Z","timestamp":1791439998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01926-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":162,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1926"],"URL":"https:\/\/doi.org\/10.1038\/s43856-026-01926-7","relation":{},"ISSN":["2730-664X"],"issn-type":[{"value":"2730-664X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"24 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"L.V. is employed by Xintela AB and holds stock options in the company. She also serves on an editorial or governing board and\/or as a member of a board of directors or committee. All other authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"522"}}