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Collagen Antibody-Induced Arthritis: A Disease-Relevant Model for Studies of Persistent Joint Pain

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TRP Channels in Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

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Abstract

Rheumatoid arthritis (RA) is a complex autoimmune disease, with a prevalence of approximately 1% in the population worldwide. RA is a chronic inflammatory disease primarily affecting joints and patients suffer from a plethora of symptoms, including pain, fatigue and stiffness. Joint pain is one of the most egregious symptoms in RA. Animal models of RA are used extensively in research to understand the pathogenesis of inflammatory arthritis and in the assessment of potential disease-modifying agents. There is an increasing need for disease-relevant animal models for pain research and several of the RA animal models that previously were not used in pain research have now been characterized for this purpose. The most commonly used RA model is the collagen-induced arthritis (CIA) model. However, it has certain disadvantages when used for pain research. Here we describe an alternative model, the collagen antibody-induced arthritis (CAIA) model to study RA-induced pain. This model has been used to investigate disease pathology for more than 10 years, but has just recently been characterized as a pain model. In comparison to CIA, more mouse strains are susceptible to CAIA and the degree of joint pathology and systemic disease is less severe, making the assessment of arthritis-associated nociceptive behavior, such as paw withdrawal from mechanical or thermal stimuli, as well as changes in normal behavior such as locomotion more easily investigated. The aim of this chapter is to describe the CAIA model and several techniques used to study inflammatory pain-like behavior.

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References

  1. Rantapaa-Dalqvist S, de Jong BA, Berglin E et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48:2741–2749

    Article  Google Scholar 

  2. Uysal H, Nandakumar KS, Kessel C et al (2010) Antibodies to citrullinated proteins: molecular interactions and arthritogenicity. Immunol Rev 233:9–33

    Article  CAS  PubMed  Google Scholar 

  3. Taylor P, Manger B, Alvaro GG et al (2010) Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. J Int Med Res 38:1213–1224

    Article  CAS  PubMed  Google Scholar 

  4. Ricci JA, Stewart WF, Chee E et al (2005) Pain exacerbation as a major source of lost productive time in US workers with arthritis. Arthritis Rheum 53:673–681

    Article  PubMed  Google Scholar 

  5. Swedish Council on Technology Assessment in Healthcare (2006) Methods of Treating Chronic Pain. Report No: 177/1þ2

    Google Scholar 

  6. Kollias G, Papadaki P, Apprailly F et al (2011) Animal models for arthritis: innovative tools for prevention and treatment. Ann Rheum Dis 70:1357–1362

    Article  PubMed  Google Scholar 

  7. Nandakumar KS (2012) Antibody mediated arthritis and new therapeutic avenues. In: Pathak Y, Benita S (eds) Antibody-Mediated Drug Delivery Systems: Concepts, Technology, and Applications. John Wiley & Sons Inc., New Jersey, pp 407–425

    Chapter  Google Scholar 

  8. Kouskoff V, Korganow AS, Duchatelle V et al (1996) Organ-specific disease provoked by systemic autoimmunity. Cell 87:811–822

    Article  CAS  PubMed  Google Scholar 

  9. Matsumoto I, Staub A, Benoist C, Mathis D (1999) Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286:1732–1735

    Article  CAS  PubMed  Google Scholar 

  10. Keffer J, Probert L, Cazlaris H et al (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10:4025–4031

    CAS  PubMed  Google Scholar 

  11. Koenders MI, Devesa I, Marijnissen RJ et al (2008) Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice. Arthritis Rheum 58:4361–3470

    Article  Google Scholar 

  12. Trentham DE, Townes AS, Kang AH (1977) Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 146:857–868

    Article  CAS  PubMed  Google Scholar 

  13. Courtenay JS, Dallman MJ, Dayan AD et al (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283:666–668

    Article  CAS  PubMed  Google Scholar 

  14. Keystone EC, Schorlemmer HU, Pope C, Allison AC (1977) Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement. Arthritis Rheum 20:1396–1401

    Article  CAS  PubMed  Google Scholar 

  15. Frasnelli ME, Tarussio D, Chobaz-Peclat V et al (2005) TLR2 modulates inflammation in zymosan-induced arthritis in mice. Arthritis Res Ther 7:370–379

    Article  Google Scholar 

  16. Vingsbo C, Sahlstrand P, Brun JG et al (1996) Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol 149:1675–1683

    CAS  PubMed  Google Scholar 

  17. Glant TT, Finnegan A, Mikecz K (2003) Proteglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics. Crit Rev Immunol 23:199–250

    Article  CAS  PubMed  Google Scholar 

  18. Kannan K, Ortmann RA, Kimpel D (2005) Animal models of rheumatoid arthritis and their relevance to human disease. Pathophysiology 12:167–181

    Article  PubMed  Google Scholar 

  19. Nandakumar KS (2010) Pathogenic antibody recognition of cartilage. Cell Tissue Res 339:213–220

    Article  CAS  PubMed  Google Scholar 

  20. Holmdahl R, Rubin K, Klareskog L et al (1986) Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum 29:400–410

    Article  CAS  PubMed  Google Scholar 

  21. Terato K, Hasty KA, Reife RA et al (1992) Induction of arthritis with monoclonal antibodies to collagen. J Immunol 148:2103–2108

    CAS  PubMed  Google Scholar 

  22. Nandakumar KS, Svensson L, Holmdahl R (2003) Collagen type II-specific monoclonal antibody-induced arthritis in mice. Am J Pathol 163:1827–1837

    Article  CAS  PubMed  Google Scholar 

  23. Nandakumar KS, Holmdahl R (2005) Efficient promotion of collagen induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis. J Immunol Methods 304: 126–136

    Article  CAS  PubMed  Google Scholar 

  24. Hutamekalin P, Saito T, Yamaki K et al (2009) Collagen antibody-induced arthritis in mice: development of a new arthritogenic 5-clone cocktail of monoclonal anti-type II collagen antibodies. J Immunol Methods 343:49–55

    Article  CAS  PubMed  Google Scholar 

  25. Christianson CA, Corr M, Firestein GS et al (2010) Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis. Pain 151:394–403

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Christianson C.A. et al. (2012) K/BxN serum transfer arthritis as a model of inflammatory joint pain. In: Luo ZD (ed) Pain Research, Methods and Protocols, Methods in Molecular Biology, Springer Science, New York

    Google Scholar 

  27. Khachigian LM (2006) Collagen-antibody-induced arthritis. Nat Protoc 1:2512–2516

    Article  CAS  PubMed  Google Scholar 

  28. Holmdahl R, Jansson L, Gullberg D et al (1985) Incidence of arthritis and autoreactivity of anti-collagen antibodies after immunization of DBA/1 mice with heterologous and autologous collagen II. Clin Exp Immunol 62:639–646

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Mogil JS, Bailey AL (2010) Sex and gender differences in pain and analgesia. Prog Brain Res 186:141–157

    PubMed  Google Scholar 

  30. Holmdahl R, Jansson L, Meyerson B et al (1987) Oestrogen induced suppression of collagen arthritis: I. Long term oestradiol treatment of DBA/1 mice reduces severity and incidence of arthritis and decreases the anti type II collagen immune response. Clin Exp Immunol 70:372–378

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Jochems C, Islander U, Erlandsson M et al (2011) Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis. Clin Exp Immunol 165:121–129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Holmdahl R, Bockermann R, Bäcklund J et al (2002) The molecular pathogenesis of ­collagen-induced arthritis in mice—a model for rheumatoid arthritis. Ageing Res Rev 1:135–147

    Article  CAS  PubMed  Google Scholar 

  33. Rowley MJ, Nandakumar KS, Holmdahl R (2008) The role of collagen antibodies in mediating arthritis. Mod Rheumatol 18:429–441

    Article  CAS  PubMed  Google Scholar 

  34. Nandakumar KS, Holmdahl R (2007) Collagen antibody induced arthritis. Methods Mol Med 136:215–223

    Article  CAS  PubMed  Google Scholar 

  35. Leffler AS, Kosek E, Lerndal T et al (2002) Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis. Eur J Pain 6:161–176

    Article  PubMed  Google Scholar 

  36. Tajino K, Matsumura K, Kosada K et al (2007) Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses. Am J Physiol Regul Integr Comp Physiol 293:2128–2135

    Article  Google Scholar 

  37. Vissers K, Meert T (2005) A behavioral and pharmacological validation of the acetone spray test in gerbils with a chronic constriction injury. Anesth Analg 101:457–464

    Article  CAS  PubMed  Google Scholar 

  38. Terato K, Harper DS, Griffiths MM et al (1995) Collagen-induced arthritis in mice: synergistic effect of E. coli lipopolysaccharide bypasses epitope specificity in the induction of arthritis with monoclonal antibodies to type II collagen. Autoimmunity 22:137–147

    Article  CAS  PubMed  Google Scholar 

  39. Wolf G, Yirmiya R, Goshen I et al (2003) Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects. Pain 104:471–480

    Article  CAS  PubMed  Google Scholar 

  40. Deleo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90:1–6

    Article  CAS  PubMed  Google Scholar 

  41. Holmdahl R et al (1998) Genetic analysis of mouse models for rheumatoid arthritis. In: Adolph KW (ed) Human Genome Methods. CRC, New York, p 215

    Google Scholar 

  42. Dixon WJ (1980) Efficient analysis of experimental observations. Ann Rev Pharmacol Toxicol 20:441–462

    Article  CAS  Google Scholar 

  43. Chaplan SR, Bach FW, Pogrel JW et al (2004) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63

    Article  Google Scholar 

  44. Vickers AJ (2005) Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data. BMC Med Res Methodol 5:35–46

    Article  PubMed Central  PubMed  Google Scholar 

  45. Leuchtweis J, Imhof AK, Montechiaro F et al (2010) Validation of the digital pressure application measurement (PAM) device for detection of primary mechanical hyperalgesia in rat and mouse antigen-induced knee joint arthritis. Methods Find Exp Clin Pharmacol 32:575–583

    Article  CAS  PubMed  Google Scholar 

  46. Walczak JS, Beaulieu P (2006) Comparison of three models of neuropathic pain in mice using a new method to assess cold allodynia: the double plate technique. Neurosci Lett 399:240–244

    Article  CAS  PubMed  Google Scholar 

  47. Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD (2010) TRPM8, but not TPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold mimetics in vivo. Pain 150:340–350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Noe J, Zimmermann K, Busserolles J et al (2009) The mechano-activated Kþ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J 28:1308–1318

    Article  Google Scholar 

  49. Dirig DM, Salami A, Rathbun ML et al (1997) Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli. J Neurosci Methods 76:183–191

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Katalin Sandor .

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Sandor, K., Nandakumar, K.S., Holmdahl, R., Svensson, C.I. (2012). Collagen Antibody-Induced Arthritis: A Disease-Relevant Model for Studies of Persistent Joint Pain. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-095-3_27

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  • DOI: https://doi.org/10.1007/978-1-62703-095-3_27

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-094-6

  • Online ISBN: 978-1-62703-095-3

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