Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Spatiotemporal gait compensations following medial collateral ligament and medial meniscus injury in the rat: correlating gait patterns to joint damage

Authors: Heidi E. Kloefkorn, Brittany Y. Jacobs, Ayomiposi M. Loye, Kyle D. Allen

Published in: Arthritis Research & Therapy | Issue 1/2015

Login to get access

Abstract

Introduction

After transection of the medial collateral ligament and medial meniscus (MCLT + MMT) in the rat, focal cartilage lesions develop over 4–6 weeks; however, sham surgery (MCLT alone) does not result in cartilage damage over a similar period. Thus, comparison of MCLT + MMT with the MCLT sham group offers an opportunity to investigate behavioral modifications related to focal cartilage and meniscus damage in the rat.

Methods

MCLT or MCLT + MMT surgery was performed in the right knees of male Lewis rats, with spatiotemporal gait patterns and hind limb sensitivity assessed at 1, 2, 4, and 6 weeks postsurgery (n = 8 rats per group per time point, n = 64 total). After the animals were euthanized, Histology was performed to assess joint damage.

Results

MCLT + MMT animals had unilateral gait compensations at early time points, but by week 6 bilateral gait compensations had developed in both the MCLT sham and MCLT + MMT groups. Conversely, heightened tactile sensitivity was detected in both MCLT sham and MCLT + MMT animals at week 1, but only the MCLT + MMT animals maintained heightened sensitivity to week 6. Cartilage lesions were found in the MCLT + MMT group but not in the MCLT sham group. Correlations could be identified between joint damage and gait changes in MCLT + MMT animals; however, the same gait changes were found with MCLT sham animals despite a lack of joint damage.

Conclusions

Combined, our data highlight a common conundrum in osteoarthritis (OA) research: Some behavioral changes correlate to cartilage damage in the OA group, but the same changes can be identified in non-OA controls. Of the behavioral changes detected, allodynia was maintained in MCLT + MMT animals but not in the MCLT sham group. However, the correlation between cartilage damage and hind limb sensitivity is relatively weak (R = −0.4498), and the range of sensitivity measures overlaps between groups. The factors driving gait abnormalities in MCLT and MCLT + MMT animals also remain uncertain. The gait modifications are similar between groups and do not appear until weeks after surgery, despite cartilage damage being focused in the MCLT + MMT group. Combined, our data highlight the need to evaluate the links between noncartilage changes and behavioral changes following joint injury in the rat.
Appendix
Available only for authorised users
Literature
1.
go back to reference Englund M, Lohmander LS. Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Arthritis Rheum. 2004;50:2811–9.CrossRefPubMed Englund M, Lohmander LS. Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Arthritis Rheum. 2004;50:2811–9.CrossRefPubMed
2.
go back to reference Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35:1756–69.CrossRefPubMed Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35:1756–69.CrossRefPubMed
3.
go back to reference Janusz MJ, Bendele AM, Brown KK, Taiwo YO, Hsieh L, Heitmeyer SA. Induction of osteoarthritis in the rat by surgical tear of the meniscus: inhibition of joint damage by a matrix metalloproteinase inhibitor. Osteoarthritis Cartilage. 2002;10:785–91. A published corrigendum appears in Osteoarthritis Cartilage. 2003;11:299.CrossRefPubMed Janusz MJ, Bendele AM, Brown KK, Taiwo YO, Hsieh L, Heitmeyer SA. Induction of osteoarthritis in the rat by surgical tear of the meniscus: inhibition of joint damage by a matrix metalloproteinase inhibitor. Osteoarthritis Cartilage. 2002;10:785–91. A published corrigendum appears in Osteoarthritis Cartilage. 2003;11:299.CrossRefPubMed
4.
go back to reference Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone. 2006;38:234–43.CrossRefPubMed Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone. 2006;38:234–43.CrossRefPubMed
5.
go back to reference Wei L, Fleming BC, Sun X, Teeple E, Wu W, Jay GD, et al. Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model. J Orthop Res. 2010;28:900–6.PubMedCentralPubMed Wei L, Fleming BC, Sun X, Teeple E, Wu W, Jay GD, et al. Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model. J Orthop Res. 2010;28:900–6.PubMedCentralPubMed
6.
go back to reference Bove SE, Laemont KD, Brooker RM, Osborn MN, Sanchez BM, Guzman RE, et al. Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia. Osteoarthritis Cartilage. 2006;14:1041–8.CrossRefPubMed Bove SE, Laemont KD, Brooker RM, Osborn MN, Sanchez BM, Guzman RE, et al. Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia. Osteoarthritis Cartilage. 2006;14:1041–8.CrossRefPubMed
7.
go back to reference Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis Cartilage. 2010;18:S24–34.CrossRefPubMed Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis Cartilage. 2010;18:S24–34.CrossRefPubMed
8.
go back to reference Allen KD, Mata BA, Gabr MA, Huebner JL, Adams Jr SB, Kraus VB, et al. Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis. Arthritis Res Ther. 2012;14:R78.PubMedCentralCrossRefPubMed Allen KD, Mata BA, Gabr MA, Huebner JL, Adams Jr SB, Kraus VB, et al. Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis. Arthritis Res Ther. 2012;14:R78.PubMedCentralCrossRefPubMed
9.
go back to reference Allen KD, Adams SB, Setton LA. Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model. Tissue Eng Part B Rev. 2010;16:81–92.PubMedCentralCrossRefPubMed Allen KD, Adams SB, Setton LA. Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model. Tissue Eng Part B Rev. 2010;16:81–92.PubMedCentralCrossRefPubMed
10.
go back to reference Allen KD, Griffin TM, Rodriguiz RM, Wetsel WC, Kraus VB, Huebner JL, et al. Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum. 2009;60:2684–93.PubMedCentralCrossRefPubMed Allen KD, Griffin TM, Rodriguiz RM, Wetsel WC, Kraus VB, Huebner JL, et al. Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen. Arthritis Rheum. 2009;60:2684–93.PubMedCentralCrossRefPubMed
12.
go back to reference Hedrick TL. Software techniques for two- and three-dimensional kinematic measurements of biological and biomimetic systems. Bioinspir Biomim. 2008;3:034001.CrossRefPubMed Hedrick TL. Software techniques for two- and three-dimensional kinematic measurements of biological and biomimetic systems. Bioinspir Biomim. 2008;3:034001.CrossRefPubMed
13.
go back to reference Allen KD, Adams Jr SB, Mata BA, Shamji MF, Gouze E, Jing L, et al. Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res. 2011;29:694–703.PubMedCentralCrossRefPubMed Allen KD, Adams Jr SB, Mata BA, Shamji MF, Gouze E, Jing L, et al. Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res. 2011;29:694–703.PubMedCentralCrossRefPubMed
14.
go back to reference Allen KD, Shamji MF, Mata BA, Gabr MA, Sinclair SM, Schmitt DO, et al. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-α antagonism. Arthritis Res Ther. 2011;13:R137.PubMedCentralCrossRefPubMed Allen KD, Shamji MF, Mata BA, Gabr MA, Sinclair SM, Schmitt DO, et al. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-α antagonism. Arthritis Res Ther. 2011;13:R137.PubMedCentralCrossRefPubMed
15.
go back to reference Hwang PY, Allen KD, Shamji MF, Jing L, Mata BA, Gabr MA, et al. Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy. Open Orthop J. 2012;6:383–91.PubMedCentralCrossRefPubMed Hwang PY, Allen KD, Shamji MF, Jing L, Mata BA, Gabr MA, et al. Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy. Open Orthop J. 2012;6:383–91.PubMedCentralCrossRefPubMed
16.
go back to reference Shamji MF, Allen KD, So S, Jing L, Adams Jr SB, Schuh R, et al. Gait abnormalities and inflammatory cytokines in an autologous nucleus pulposus model of radiculopathy. Spine. 2009;34:648–54.PubMedCentralCrossRefPubMed Shamji MF, Allen KD, So S, Jing L, Adams Jr SB, Schuh R, et al. Gait abnormalities and inflammatory cytokines in an autologous nucleus pulposus model of radiculopathy. Spine. 2009;34:648–54.PubMedCentralCrossRefPubMed
17.
go back to reference Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53:55–63.CrossRefPubMed Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53:55–63.CrossRefPubMed
18.
go back to reference Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 2006;14:13–29.CrossRefPubMed Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 2006;14:13–29.CrossRefPubMed
19.
go back to reference Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS. The relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: the role of catastrophizing. Pain. 2000;87:325–34.CrossRefPubMed Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS. The relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: the role of catastrophizing. Pain. 2000;87:325–34.CrossRefPubMed
20.
go back to reference Chan WP, Huang GS, Hsu SM, Chang YC, Ho WP. Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain. Skeletal Radiol. 2008;37:917–22.PubMedCentralCrossRefPubMed Chan WP, Huang GS, Hsu SM, Chang YC, Ho WP. Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain. Skeletal Radiol. 2008;37:917–22.PubMedCentralCrossRefPubMed
21.
go back to reference Peat G, Greig J, Wood L, Wilkie R, Thomas E, Croft P. Diagnostic discordance: we cannot agree when to call knee pain ‘osteoarthritis’. Fam Pract. 2005;22:96–102.CrossRefPubMed Peat G, Greig J, Wood L, Wilkie R, Thomas E, Croft P. Diagnostic discordance: we cannot agree when to call knee pain ‘osteoarthritis’. Fam Pract. 2005;22:96–102.CrossRefPubMed
22.
go back to reference Bedson J, Croft PR. The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet Disord. 2008;9:116.PubMedCentralCrossRefPubMed Bedson J, Croft PR. The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet Disord. 2008;9:116.PubMedCentralCrossRefPubMed
23.
go back to reference Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol. 2000;27:1513–7.PubMed Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol. 2000;27:1513–7.PubMed
24.
go back to reference Golightly YM, Allen KD, Stechuchak KM, Coffman CJ, Keefe FJ. Associations of coping strategies with diary based pain variables among Caucasian and African American patients with osteoarthritis. Int J Behav Med. 2015;22:101–8.CrossRefPubMed Golightly YM, Allen KD, Stechuchak KM, Coffman CJ, Keefe FJ. Associations of coping strategies with diary based pain variables among Caucasian and African American patients with osteoarthritis. Int J Behav Med. 2015;22:101–8.CrossRefPubMed
25.
go back to reference Keefe FJ, Caldwell DS, Queen KT, Gil KM, Martinez S, Crisson JE, et al. Pain coping strategies in osteoarthritis patients. J Consult Clin Psychol. 1987;55:208–12.CrossRefPubMed Keefe FJ, Caldwell DS, Queen KT, Gil KM, Martinez S, Crisson JE, et al. Pain coping strategies in osteoarthritis patients. J Consult Clin Psychol. 1987;55:208–12.CrossRefPubMed
26.
go back to reference Somers TJ, Keefe FJ, Pells JJ, Dixon KE, Waters SJ, Riordan PA, et al. Pain catastrophizing and pain-related fear in osteoarthritis patients: relationships to pain and disability. J Pain Symptom Manage. 2009;37:863–72.PubMedCentralCrossRefPubMed Somers TJ, Keefe FJ, Pells JJ, Dixon KE, Waters SJ, Riordan PA, et al. Pain catastrophizing and pain-related fear in osteoarthritis patients: relationships to pain and disability. J Pain Symptom Manage. 2009;37:863–72.PubMedCentralCrossRefPubMed
27.
go back to reference Hunter DJ, McDougall JJ, Keefe FJ. The symptoms of osteoarthritis and the genesis of pain. Med Clin North Am. 2009;93:83–100.CrossRefPubMed Hunter DJ, McDougall JJ, Keefe FJ. The symptoms of osteoarthritis and the genesis of pain. Med Clin North Am. 2009;93:83–100.CrossRefPubMed
28.
go back to reference Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain. 2004;112:83–93.CrossRefPubMed Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain. 2004;112:83–93.CrossRefPubMed
29.
go back to reference Laurin J, Dousset E, Mesure S, Decherchi P. Neuromuscular recovery pattern after medial collateral ligament disruption in rats. J Appl Physiol. 2009;107:98–104.CrossRefPubMed Laurin J, Dousset E, Mesure S, Decherchi P. Neuromuscular recovery pattern after medial collateral ligament disruption in rats. J Appl Physiol. 2009;107:98–104.CrossRefPubMed
30.
go back to reference Chamberlain CS, Leiferman EM, Frisch KE, Brickson SL, Murphy WL, Baer GS, et al. Interleukin expression after injury and the effects of interleukin-1 receptor antagonist. PLoS One. 2013;8, e71631.PubMedCentralCrossRefPubMed Chamberlain CS, Leiferman EM, Frisch KE, Brickson SL, Murphy WL, Baer GS, et al. Interleukin expression after injury and the effects of interleukin-1 receptor antagonist. PLoS One. 2013;8, e71631.PubMedCentralCrossRefPubMed
31.
go back to reference Roubille C, Raynauld JP, Abram F, Paiement P, Dorais M, Delorme P, et al. The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study. Arthritis Res Ther. 2014;16:507.PubMedCentralCrossRefPubMed Roubille C, Raynauld JP, Abram F, Paiement P, Dorais M, Delorme P, et al. The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study. Arthritis Res Ther. 2014;16:507.PubMedCentralCrossRefPubMed
32.
go back to reference Thakur M, Dickenson AH, Baron R. Osteoarthritis pain: nociceptive or neuropathic? Nat Rev Rheumatol. 2014;10:374–80.CrossRefPubMed Thakur M, Dickenson AH, Baron R. Osteoarthritis pain: nociceptive or neuropathic? Nat Rev Rheumatol. 2014;10:374–80.CrossRefPubMed
33.
go back to reference McDougall JJ, Watkins L, Li Z. Vasoactive intestinal peptide (VIP) is a modulator of joint pain in a rat model of osteoarthritis. Pain. 2006;123:98–105.CrossRefPubMed McDougall JJ, Watkins L, Li Z. Vasoactive intestinal peptide (VIP) is a modulator of joint pain in a rat model of osteoarthritis. Pain. 2006;123:98–105.CrossRefPubMed
34.
go back to reference McDougall JJ, Bray RC, Sharkey KA. Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat Rec. 1997;248:29–39.CrossRefPubMed McDougall JJ, Bray RC, Sharkey KA. Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat Rec. 1997;248:29–39.CrossRefPubMed
35.
36.
go back to reference Fu SC, Cheuk YC, Hung LK, Chan KM. Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis. Osteoarthritis Cartilage. 2012;20:1409–16.CrossRefPubMed Fu SC, Cheuk YC, Hung LK, Chan KM. Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis. Osteoarthritis Cartilage. 2012;20:1409–16.CrossRefPubMed
37.
go back to reference Sterling M, Jull G, Wright A. The effect of musculoskeletal pain on motor activity and control. J Pain. 2001;2:135–45.CrossRefPubMed Sterling M, Jull G, Wright A. The effect of musculoskeletal pain on motor activity and control. J Pain. 2001;2:135–45.CrossRefPubMed
Metadata
Title
Spatiotemporal gait compensations following medial collateral ligament and medial meniscus injury in the rat: correlating gait patterns to joint damage
Authors
Heidi E. Kloefkorn
Brittany Y. Jacobs
Ayomiposi M. Loye
Kyle D. Allen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0791-2

Other articles of this Issue 1/2015

Arthritis Research & Therapy 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.