Unrestricted Weight Bearing as a Method for Assessment of Nociceptive Behavior in a Model of Tibiofemoral Osteoarthritis in Rats

DOI: 10.4236/jbbs.2013.33030   PDF   HTML   XML   3,536 Downloads   5,939 Views   Citations


Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. The aim of this study was therefore to characterize the Tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P < 0.05), 21 (P < 0.001) and 28 (P < 0.001) days post intra-articular injections of MIA compared to control. These alterations were attenuated by morphine 1 hour post administration compared to baseline but were not affected by naproxen. Conclusion: This study indicated that unrestricted WB assessed by the Tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. Therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.

Share and Cite:

L. Gregersen, T. Røsland, L. Arendt-Nielsen, G. Whiteside and M. Hummel, "Unrestricted Weight Bearing as a Method for Assessment of Nociceptive Behavior in a Model of Tibiofemoral Osteoarthritis in Rats," Journal of Behavioral and Brain Science, Vol. 3 No. 3, 2013, pp. 306-314. doi: 10.4236/jbbs.2013.33030.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. W. J. Bijlsma, F. Berenbaum and F. P. J. G. Lafeber, “Osteoarthritis: An Update with Relevance for Clinical Practice,” Lancet, Vol. 377, No. 9783, 2011, pp. 2115-2126. doi:10.1016/S0140-6736(11)60243-2
[2] H. Bliddal, L. Bilde, A. Ankjr-Jensen, T. Demontis, K. E. Jensen, H. Lund, A. Odgaard, J. O. Rasmussen, H. Rgind, H. Schrder and K. L. Srensen, “Referenceprogram for Behandling af Knartrose,” 2007. http://www.sst.dk/publ/Publ2007/PLAN/SfR/Refprg_knaeartrose.pdf
[3] J. R. Hochman, M. R. French, S. L. Bermingham and G. A. Hawker, “The Nerve of Osteoarthritis Pain,” Arthritis Care & Research, Vol. 62, No. 7, 2010, pp. 1019-1023. doi:10.1002/acr.20142
[4] D. T. Felson, “Developments in the Clinical Understanding of Osteoarthritis,” Arthritis Research & Therapy, Vol. 11, No. 1, 2009, pp. 203-214. doi:10.1186/ar2531
[5] M. B. Goldring and S. R. Goldring, “Articular Cartilage and Subchondral Bone in the Pathogenesis of Osteoarthritis,” Annals of the New York Academy of Sciences, Vol. 1192, No. 1, 2010, pp. 230-237. doi:10.1111/j.1749-6632.2009.05240.x
[6] H. G. Schiable, “Spinal Mechanisms Contributing to Joint Pain,” Novartis Foundation Symposia, Vol. 260, 2004, pp. 4-22. doi:10.1002/0470867639.ch2
[7] L. Arendt-Nielsen, H. Nie, M. B. Laursen, B. S. Laursen, P. Madeleine, O. H. Simonsen and T. Graven-Nielsen, “Sensitization in Patients with Painful Knee Osteoarthritis,” Pain, Vol. 149, No. 3, 2010, pp. 573-581. doi:10.1016/j.pain.2010.04.003
[8] J. S. Lawrence, J. M. Bremner and F. Bier, “Osteoarthrosis. Prevalence in the Population and Relationship between Symptoms and X-Ray Changes,” Annals of the Rheumatic Diseases, Vol. 25, No. 1, 1966, pp. 1-24.
[9] S. E. Bove, S. L. Calcaterra, R. M. Brooker, C. M. Huber, R. E. Guzman, P. L. Juneau, D. J. Schrier and K. S. Kilgore, “Weight Bearing as a Measure of Disease Progression and Efficacy of Anti-Inflammatory Compounds in a Model of Monosodium Iodoacetate-Induced Osteoarthritis,” Osteoarthritis Cartilage, Vol. 11, No. 11, 2003, pp. 821-830. doi:10.1016/S1063-4584(03)00163-8
[10] Y. Lee, M. Pai, J. D. Brederson, D. Wilcox, G. Hsieh, M. F. Jarvis and R. S. Bitner, “Monosodium IodoacetateInduced Joint Pain Is Associated with Increased Phosphorylation of Mitogen Activated Protein Kinases in the Rat Spinal Cord,” Molecular Pain, Vol. 7, 2011, pp. 3949. doi:10.1186/1744-8069-7-39
[11] J. D. Pomonis, J. M. Boulet, S. L. Gottshall, S. Phillips, R. Sellers, T. Bunton and K. Walker, “Development and Pharmacological Characterization of a Rat Model of Osteoarthritis Pain,” Pain, Vol. 114, No. 3, 2005, pp. 339-346. doi:10.1016/j.pain.2004.11.008
[12] S. Orita, T. Ishikawa, M. Miyagi, N. Ochial, G. Inoue, Y. Eguchi, H. Kamoda, G. Arai, T. Toyone, Y. Aoki, T. Kobu, K. Takekazu and S. Ohtori, “Pain-Related Sensory Innervation in Monoiodoacetate-Induced Osteoarthritis in Rat Knee That Gradually Develops Neuronal Injury in Addition to Inflammatory Pain,” BMC Musculoskeletal Disorders, Vol. 12, 2011, pp. 134-146. doi:10.1186/1471-2474-12-134
[13] M. Zimmermann, “Ethical Guidelines for Investigations of Experimental Pain in Conscious Animals,” Pain, Vol. 16, No. 2, 1983, pp. 109-110. doi:10.1016/0304-3959(83)90201-4
[14] P. Chandran, M. Pai, E. A. Blomme, G. C. Hsieh, M. W. Decker and P. Honore, “Pharmacological Modulation of Movement-Evoked Pain in a Rat Model of Osteoarthritis,” European Journal of Pharmacology, Vol. 613, No. 1-3, 2009, pp. 39-54. doi:10.1016/j.ejphar.2009.04.009
[15] R. Combe, S. Bramwell and M. J. Field, “The Monosodium Iodoacetate Model of Osteoarthritis: A Model of Chronic Nociceptive Pain in Rats?” Neuroscience Letters, Vol. 370, No. 2-3, 2004, pp. 236-240. doi:10.1016/j.neulet.2004.08.023
[16] K. L. Chu, P. Chandran, S. K. Joshi, M. F. Jarvis, P. R. Kym and S. McGaraughty, “TRPV1-Related Modulation of Spinal Neuronal Activity and Behavior in a Rat Model of Osteoarthritic Pain,” Brain Research, Vol. 1369, 2011, pp. 158-166. doi:10.1016/j.brainres.2010.10.101
[17] E. Schtt, O. G. Berge, K. ngeby-Mller, G. Hammarstrm, C. J. Dalsgaard and E. Brodin, “Weight Bearing as an Objective Measure of Arthritic Pain in the Rat,” Journal of Pharmacological and Toxicological Methods, Vol. 31, No. 2, 1994, pp. 79-83. doi:10.1016/1056-8719(94)90046-9
[18] B. S. Boyd, C. Puttlitz, L. J. Noble-Haeusslein, C. M. John, A. Trivedi and K. S. Topp, “Deviations in Gait Pattern in Experimental Models of Hindlimb Paresis Shown by a Novel Pressure Mapping System,” Journal of Neuroscience Research, Vol. 85, No. 10, 2007, pp. 22722283. doi:10.1002/jnr.21366
[19] H. Rashid, Y. Theberge. S. J. Elmes, M. N. Perkins and F. McIntosh, “Pharmacological Validation of Early and Late Phase of Rat Monoiodoacetate Model Using the Tekscan System,” European Journal of Pain, Vol. 17, No. 2, 2012, pp. 210-222. doi:10.1002/j.1532-2149.2012.00176.x
[20] J. Ferreira-Gomes, S. Adaes and J. M. Castro-Lopes, “Assessment of Movement-Evoked Pain in Osteoarthritis by the Knee-Bend and Catwalk Tests: A Clinically Relevant Study,” The Journal of Pain, Vol. 9, No. 10, 2008, pp. 945-954. doi:10.1016/j.jpain.2008.05.012
[21] S. S. Min, J. S. Han, Y. I. Kim, H. S. Na, Y. W. Yoon, S. K. Hong and H. C. Han, “A Novel Method for Convenient Assessment of Arthritic Pain in Voluntarily Walking Rats,” Neuroscience Letters, Vol. 308, No. 2, 2001, pp. 95-98. doi:10.1016/S0304-3940(01)01983-8
[22] P. Tétreault, M. Dansereau, L. Doré-Savard, N. Beaudet and P. Sarret, “Weight Bearing Evaluation in Inflamematory, Neuropathic and Cancer Chronic Pain in Freely Moving Rats,” Physiology & Behavior, Vol. 104, No. 3, 2011, pp. 495-502. doi:10.1016/j.physbeh.2011.05.015
[23] K. A. Clarke, S. A. Heitmeyer, A. G. Smith and Y. O. Taiwo, “Gait Analysis in a Rat Model of Osteoarthrosis,” Physiology & Behavior, Vol. 62, No. 5, 1997, pp. 951-954. doi:10.1016/S0031-9384(97)00022-X
[24] J. Fernihough, C. Gentry, M. Malcangio, A. Fox, J. Rediske, T. Pellas, B. Kidd, S. Bevan and J. Winter, “Pain Related Behavior in Two Models of Osteoarthritis in the Rat Knee,” Pain, Vol. 112, No. 1-2, 2004, pp. 1-11. doi:10.1016/j.pain.2004.08.004
[25] A. M. Fendrick and B. P. Greenberg, “A Review of the Benefits and Risks of Nonsteroidal Anti-Inflammatory Drugs in the Management of Mild-to-Moderate Osteoarthritis,” Osteopathic Medicine and Primary Care, Vol. 3, 2009, pp. 1-7. doi:10.1186/1750-4732-3-1
[26] T. W. Towheed and M. C. Hochberg, “A Systemic Review of Randomized Controlled Trials of Pharmacological Therapy in Osteoarthritis of the Knee, with an Emphasis on Trial Methodology,” Seminars in Arthritis and Rheumatism, Vol. 26, No. 5, 1997, pp. 755-770. doi:10.1016/S0049-0172(97)80043-1
[27] J. Ferreira-Gomes, S. Adaes, M. Mendonca and J. M. Castro-Lopes, “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,” Pharmacology Biochemistry and Behavior, Vol. 101, No. 4, 2012, pp. 617-624. doi:10.1016/j.pbb.2012.03.003
[28] J. R. Caldwell, R. J. Rapoport, J. C. Davis, H. L. Offenberg, H. W. Marker, S. H. Roth, W. Yuan, L. Eliot, N. Babul and P. M. Lynch, “Efficacy and Safety of a OnceDaily Morphine Formulation in Chronic, Moderate-toSevere Osteoarthritis Pain: Results from a Randomized, Placebo-Controlled, Double-Blind Trial and An open-Label Extension Trial,” Journal of Pain and Symptom Management, Vol. 23, No. 4, 2002, pp. 278-291. doi:10.1016/S0885-3924(02)00383-4
[29] I. Robinson, B. Sargent and J. P. Hatcher, “Use of Dynamic Weight Bearing as a Novel End-Point for the Assessment of Freund’s Complete Adjuvant Induced Hypersensitivity in Mice,” Neuroscience Letters, Vol. 524, No. 2, 2012, pp. 107-110. doi:10.1016/j.neulet.2012.07.017

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.