Animal Models for the Study of Bone-Derived Pain

  • Austen L. Thompson
  • Tally M. Largent-Milnes
  • Todd W. VanderahEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1914)


Bone pain is a prevalent issue in society today and also is one of the hardest types of pain to control. Pain originating in the bone can be caused by many different entities including metastatic and primary neoplasm, fracture, osteoarthritis as well as numerous other metabolic disorders. In this chapter we describe the methods and protocols that currently are accepted and validated for the study of bone pain in models of metastatic cancer, bicortical fracture and osteoarthritis. These animal models provide invaluable information as to the nature of bone pain and give rise to potential new targets for its treatment and management.

Key words

Bone pain Cancer pain Osteoarthritis Fracture Metastatic disease 


  1. 1.
    Ibrahim T, Mercatali L, Amadori D (2013) Bone and cancer: the osteoncology. Clin Cases Miner Bone Metab 10(2):121–123PubMedPubMedCentralGoogle Scholar
  2. 2.
    Felson DT (2006) Clinical practice. Osteoarthritis of the knee. N Engl J Med 354(8):841–848CrossRefGoogle Scholar
  3. 3.
    Goldring MB, Goldring SR (2007) Osteoarthritis. J Cell Physiol 213(3):626–634CrossRefGoogle Scholar
  4. 4.
    Nersesyan H, Slavin KV (2007) Current aproach to cancer pain management: availability and implications of different treatment options. Ther Clin Risk Manag 3(3):381–400PubMedPubMedCentralGoogle Scholar
  5. 5.
    King T et al (2007) Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain 132(1-2):154–168CrossRefGoogle Scholar
  6. 6.
    Lozano-Ondoua AN et al (2010) A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sci 86(17–18):646–653CrossRefGoogle Scholar
  7. 7.
    Lozano-Ondoua AN, Symons-Liguori AM, Vanderah TW (2013) Cancer-induced bone pain: mechanisms and models. Neurosci Lett 557(Pt A):52–59CrossRefGoogle Scholar
  8. 8.
    Arguello F, Baggs RB, Frantz CN (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48(23):6876–6881PubMedGoogle Scholar
  9. 9.
    Honore P et al (2000) Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6(5):521–528CrossRefGoogle Scholar
  10. 10.
    Schwei MJ et al (1999) Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci 19(24):10886–10897CrossRefGoogle Scholar
  11. 11.
    Medhurst SJ et al (2002) A rat model of bone cancer pain. Pain 96(1-2):129–140CrossRefGoogle Scholar
  12. 12.
    Slosky LM, Largent-Milnes TM, Vanderah TW (2015) Use of animal models in understanding cancer-induced bone pain. Cancer Growth Metastasis 8(Suppl 1):47–62PubMedPubMedCentralGoogle Scholar
  13. 13.
    Majuta LA et al (2015) Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor. Pain 156(1):157–165CrossRefGoogle Scholar
  14. 14.
    Pfuntner A, Wier LM, Stocks C (2006) Most frequent procedures performed in U.S. Hospitals, 2011: statistical brief #165, in Healthcare Cost and Utilization Project (HCUP) statistical briefs, Rockville, MDGoogle Scholar
  15. 15.
    Kortebein P et al (2007) Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297(16):1772–1774CrossRefGoogle Scholar
  16. 16.
    English KL, Paddon-Jones D (2010) Protecting muscle mass and function in older adults during bed rest. Curr Opin Clin Nutr Metab Care 13(1):34–39CrossRefGoogle Scholar
  17. 17.
    Abramson SB, Attur M (2009) Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther 11(3):227CrossRefGoogle Scholar
  18. 18.
    Schwartz ST, Zimmermann B (1999) Update on osteoarthritis. Med Health R I 82(9):321–324PubMedGoogle Scholar
  19. 19.
    Kalbhen DA (1987) Chemical model of osteoarthritis--a pharmacological evaluation. J Rheumatol 14:130–131PubMedGoogle Scholar
  20. 20.
    Honore P et al (2009) Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia. Pain 142(1-2):27–35CrossRefGoogle Scholar
  21. 21.
    Combe R, Bramwell S, Field MJ (2004) The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats? Neurosci Lett 370(2-3):236–240CrossRefGoogle Scholar
  22. 22.
    Ruan MZ et al (2013) Quantitative imaging of murine osteoarthritic cartilage by phase-contrast micro-computed tomography. Arthritis Rheum 65(2):388–396CrossRefGoogle Scholar
  23. 23.
    Bove SE et al (2003) Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr Cartil 11(11):821–830CrossRefGoogle Scholar
  24. 24.
    Lozano-Ondoua AN et al (2013) Disease modification of breast cancer-induced bone remodeling by cannabinoid 2 receptor agonists. J Bone Miner Res 28(1):92–107CrossRefGoogle Scholar
  25. 25.
    Chaplan SR et al (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53(1):55–63CrossRefGoogle Scholar
  26. 26.
    Dixon WJ (1980) Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 20:441–462CrossRefGoogle Scholar
  27. 27.
    Chartier SR et al (2014) Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain. Pain 155(11):2323–2336CrossRefGoogle Scholar
  28. 28.
    Hargreaves K et al (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32(1):77–88CrossRefGoogle Scholar
  29. 29.
    Liu P et al (2011) Ongoing pain in the MIA model of osteoarthritis. Neurosci Lett 493(3):72–75CrossRefGoogle Scholar
  30. 30.
    Chandran P et al (2009) Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis. Eur J Pharmacol 613(1–3):39–45CrossRefGoogle Scholar
  31. 31.
    Ivanavicius SP et al (2007) Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain 128(3):272–282CrossRefGoogle Scholar
  32. 32.
    Ruan MZ et al (2013) Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model. Osteoarthr Cartil 21(9):1355–1364CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Austen L. Thompson
    • 1
  • Tally M. Largent-Milnes
    • 1
  • Todd W. Vanderah
    • 1
    Email author
  1. 1.Department of Pharmacology, College of MedicineUniversity of ArizonaTucsonUSA

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