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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1560265
Significant hindlimb static weight-bearing asymmetry persists for 40weeks in a longitudinal study in two widely used rat models of surgically induced osteoarthritis knee pain
Provisionally accepted- 1 Centre for Integrated Preclinical Drug Development, School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, Queensland, Australia
- 2 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, Biberach an der Riss, Baden-Württemberg, Germany
Unrelenting osteoarthritis (OA) knee pain is the primary reason patients seek treatment that may ultimately result in knee replacement surgery. Although the anterior cruciate ligament transection (ACLT) and the ACLT plus medial meniscus (MMx) surgery-induced rat models of OA knee pain are well-characterized histologically, reports on changes in pain-like behaviors that persist longterm, are scant. To address this knowledge gap, we conducted a 40-week longitudinal study using these models in male Sprague-Dawley rats. Hindlimb static weight-bearing asymmetry was assessed using the incapacitance test. Von Frey filaments and an Analgesy-Meter were used to measure paw withdrawal thresholds (PWTs) and paw pressure thresholds (PPTs) respectively in the hindpaws. Our findings show significant, reproducible and long-lasting static weight-bearing asymmetry in the hindlimbs of both models (but not the sham-control group) for the 40-week study duration. Significant mechanical hypersensitivity developed in the ipsilateral hindpaws of the ACLT+MMx model (PWTs ≤8g) which reversed spontaneously by 8-12-weeks. In the ACLT and the sham-groups, significant mechanical hypersensitivity did not develop in the ipsilateral hindpaws. In conclusion, hindlimb static weightbearing asymmetry is a long-lasting, significant pain behavioral endpoint in these models suitable for assessing novel disease-modifying OA therapeutics and/or analgesic drug candidates aimed at alleviating unrelenting chronic OA knee pain in patients.
Keywords: Osteoarthritis Knee Pain, static weight bearing asymmetry, pain behavior in rat, anterior cruciate ligament transection (ACLT), ACLT + medial meniscus surgery (MMx)
Received: 14 Jan 2025; Accepted: 31 Mar 2025.
Copyright: © 2025 Kuo, Raboczyj, Nicholson, Corradini and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Maree Therese Smith, Centre for Integrated Preclinical Drug Development, School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, 4072, Queensland, Australia
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