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Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain

Ter Heegde, F; Luiz, AP; Santana-Varela, S; Chessell, IP; Welsh, F; Wood, JN; Chenu, C; (2019) Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain. Arthritis & Rheumatology , 71 (7) pp. 1078-1088. 10.1002/art.40835. Green open access

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Abstract

OBJECTIVE: Mechanisms responsible for osteoarthritic pain remain poorly understood and current analgesic therapies are often insufficient. We have characterized and pharmacologically tested the pain phenotype of a non-invasive mechanical joint loading (MJL) model of osteoarthritis thus providing an alternative murine model for osteoarthritic pain. METHODS: The right knees of male mice (12-week-old, C57BL/6) were loaded at 9N or 11N (40 cycles, three times/week for two weeks). Behavioural measurements of limb disuse, mechanical and thermal hypersensitivity were acquired before MJL and monitored for six weeks post-loading. The severity of articular cartilage lesions was determined post-mortem with the OARSI grading scheme. Furthermore, 9N-loaded mice were treated for four weeks with diclofenac (10mg/kg), gabapentin (100mg/kg) or anti-Nerve Growth Factor (3mg/kg). RESULTS: Mechanical hypersensitivity and weight-bearing worsened significantly in 9N- and 11N-loaded mice two weeks post-loading compared to baseline values and non-loaded controls. Maximum OA scores of ipsilateral knees confirmed increased cartilage lesions in 9N- (2.8±0.2) and 11N-loaded (5.3±0.3) mice compared to non-loaded controls (1.0±0.0). Gabapentin and diclofenac restored pain behaviours to baseline values after two weeks of daily treatment, with gabapentin being more effective than diclofenac. A single injection of anti-NGF alleviated nociception two days after treatment and remained effective for two weeks with a second dose inducing stronger and more prolonged analgesia. CONCLUSION: Our results show that MJL induces OA lesions and a robust pain phenotype that can be reversed using analgesics known to alleviate OA pain in patients. This establishes the use of MJL as an alternative model for osteoarthritic pain.

Type: Article
Title: Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/art.40835
Publisher version: https://doi.org/10.1002/art.40835
Language: English
Additional information: © 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10069398
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