Skip to main content

Molecular Temporomandibular Joint Pain Biomarkers

  • Chapter
  • First Online:
Orofacial Pain Biomarkers

Abstract

This chapter covers immunological markers for inflammatory types of temporomandibular joint (TMJ) pain. The specific biological relevance or clinical value of biomarkers in TMJ pain is, however, so far insufficiently investigated. There are studies that indicate candidate biomarkers for diagnostic or prognostic purposes in diseases like rheumatoid arthritis and psoriatic arthritis. This chapter discusses available knowledge regarding cytokines, cytokine receptors, serotonin, prostaglandin E2, and glutamate in relation to diagnosis, prognosis, and treatment of TMJ inflammatory pain.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Voog U, Alstergren P, Leibur E, Kallikorm R, Kopp S. Impact of temporomandibular joint pain on activities of daily living in patients with rheumatoid arthritis. Acta Odontol Scand. 2003;61(5):278–82.

    Article  PubMed  Google Scholar 

  2. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–147.

    PubMed  Google Scholar 

  3. Dinarello CA. IL-1, IL-1beta, IL-1 receptor type I, IL-1 receptor type II. In: Oppenheim JJ, Feldmann M, Durum SK, Hirano T, Vilcek J, Nicola NA, editors. Cytokine reference. Burlington: Academic; 2000.

    Google Scholar 

  4. Koenders MI, Joosten LA, van den Berg WB. Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis. Ann Rheum Dis. 2006;65 Suppl 3:29–33.

    Google Scholar 

  5. Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007;117:289–96.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dinarello CA. The biological properties of interleukin-1. Euro Cytokine Network. 1994;5:517–31.

    Google Scholar 

  7. Schutze S, Machleidt T, Kronke M. Mechanisms of tumor necrosis factor action. Semin Oncol. 1992;19:16–24.

    PubMed  Google Scholar 

  8. Jouvenne P, Vannier E, Dinarello CA, Miossec P. Elevated levels of soluble interleukin-1 receptor type II and interleukin-1 receptor antagonist in patients with chronic arthritis: correlations with markers of inflammation and joint destruction. Arthritis Rheum. 1998;41:1083–9.

    Article  PubMed  Google Scholar 

  9. Ahmed N, Catrina AI, Alyamani AO, Mustafa H, Alstergren P. Deficient cytokine control modulates temporomandibular joint pain in rheumatoid arthritis. Eur J Oral Sci. 2015;123:235–41.

    Article  PubMed  Google Scholar 

  10. Türp JC, Sommer C, Hugger A (eds): The puzzle of orofacial pain. Integrating research into clinical management. Pain Headache. Basel: Karger, 2007;15: 28–43. doi: 10.1159/000101966.

  11. Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain. 1995;63:289–302.

    Article  PubMed  Google Scholar 

  12. DeLeo JA, Colburn RW, Nichols M, Malhotra A. Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J Interf Cytokine Res. 1996;16:695–700.

    Article  Google Scholar 

  13. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1998;12:123–37.

    Article  Google Scholar 

  14. Laye S, Bluthe RM, Kent S, Combe C, Medina C, Parnet P, Kelley K, Dantzer R. Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS. Am J Phys. 1995;268:R1327–31.

    Google Scholar 

  15. Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 2006;203:1623–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Alstergren P, Larsson PT, Kopp S. Successful treatment with multiple intra-articular injections of infliximab in a patient with psoriatic arthritis. Scand J Rheumatol. 2008;37(2):155–7.

    Article  PubMed  Google Scholar 

  17. Feldmann M, Brennan FM, Williams RO, Cope AP, Gibbons DL, Katsikis PD, Maini RN. Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in rheumatoid arthritis. Progress Growth Factor Res. 1992;4:247–55.

    Article  Google Scholar 

  18. Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184–7.

    Article  PubMed  Google Scholar 

  19. Aggarwal BB, Samanta A, Feldmann M. TNF receptors. In: Oppenheim JJ, Feldmann M, Durum SK, Hirano T, Vilcek J, Nicola NA, editors. Cytokine reference. Burlington: Academic. 2000.

    Google Scholar 

  20. Alstergren P, Kopp S. Insufficient endogenous control of tumor necrosis factor-alpha contributes to temporomandibular joint pain and tissue destruction in rheumatoid arthritis. J Rheumatol. 2006;33:1734–9.

    PubMed  Google Scholar 

  21. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340:253–9.

    Article  PubMed  Google Scholar 

  22. Junger H, Sorkin LS. Nociceptive and inflammatory effects of subcutaneous TNFalpha. Pain. 2000;85:145–51.

    Article  PubMed  Google Scholar 

  23. Cunha TM, Verri WA, Silva JS, Poole S, Cunha FQ, Ferreira SH. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. PNAS. 2005;102:1755–60.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Inglis JJ, Nissim A, Lees DM, Hunt SP, Chernajovsky Y, Kidd BL. The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. Arthritis Res Ther. 2005;7:R807–16.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sommer C, Schmidt C, George A. Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1. Exp Neurol. 1998;151:138–42.

    Article  PubMed  Google Scholar 

  26. Li Y, Ji A, Weihe E, Schafer MK. Cell-specific expression and lipopolysaccharide-induced regulation of tumor necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion. J Neurosci. 2004;24:9623–31.

    Article  PubMed  Google Scholar 

  27. Fredriksson L, Alstergren P, Kopp S. Tumor necrosis factor-alpha in temporomandibular joint synovial fluid predicts treatment effects on pain by intra-articular glucocorticoid treatment. Mediators Inflamm. 2006;2006:59425.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Partsch G, Steiner G, Leeb BF, Dunky A, Broll H, Smolen JS. Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid. J Rheumatol. 1997;24:518–23.

    PubMed  Google Scholar 

  29. Nordahl S, Alstergren P, Kopp S. Tumor necrosis factor-alpha in synovial fluid and plasma from patients with chronic connective tissue disease and its relation to temporomandibular joint pain. J Oral Maxillofac Surg. 2000;58:525–30.

    Article  PubMed  Google Scholar 

  30. Sandler NA, Buckley MJ, Cillo JE, Braun TW. Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements. J Oral Maxillofac Surg. 1998;56:534–43.

    Article  PubMed  Google Scholar 

  31. Takahashi T, Kondoh T, Fukuda M, Yamazaki Y, Toyosaki T, Suzuki R. Proinflammatory cytokines detectable in synovial fluids from patients with temporomandibular disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:135–41.

    Article  PubMed  Google Scholar 

  32. Roux-Lombard P, Punzi L, Hasler F, Bas S, Todesco S, Gallati H, Guerne PA, Dayer JM. Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum. 1993;36:485–9.

    Article  PubMed  Google Scholar 

  33. Ruschen S, Lemm G, Warnatz H. Spontaneous and LPS-stimulated production of intracellular IL-1 beta by synovial macrophages in rheumatoid arthritis is inhibited by IFN-gamma. Clin Exp Immunol. 1989;76:246–51.

    PubMed  PubMed Central  Google Scholar 

  34. Barbe MF, Barr AE. Inflammation and the pathophysiology of work-related musculoskeletal disorders. Brain Behav Immun. 2006;20:423–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Muegge K, Vila M, Gusella GL, Musso T, Herrlich P, Stein B, Durum SK. Interleukin 1 induction of the c-jun promoter. PNAS. 1993;90:7054–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Muegge K, Williams TM, Kant J, Karin M, Chiu R, Schmidt A, Siebenlist U, Young HA, Durum SK. Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. Science. 1989;246:249–51.

    Article  PubMed  Google Scholar 

  37. Arend WP, Malyak M, Smith MF, Whisenand TD, Slack JL, Sims JE, Giri JG, Dower SK. Binding of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids. J Immunol. 1994;153:4766–74.

    PubMed  Google Scholar 

  38. Dower SK, Fanslow W, Jacobs C, Waugh S, Sims JE, Widmer MB. Interleukin-I antagonists. Therapeutic Immunol. 1994;1:113–22.

    Google Scholar 

  39. Sims JE, Giri JG, Dower SK. The two interleukin-1 receptors play different roles in IL-1 actions. Clin Immunol Immunopathol. 1994;72:9–14.

    Article  PubMed  Google Scholar 

  40. Alstergren P, Benavente C, Kopp S. Interleukin-1beta, interleukin-1 receptor antagonist, and interleukin-1 soluble receptor II in temporomandibular joint synovial fluid from patients with chronic polyarthritides. J Oral Maxillofac Surg. 2003;61:1171–8.

    Article  PubMed  Google Scholar 

  41. Fukuoka H, Kawatani M, Hisamitsu T, Takeshige C. Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 beta in the rat. Brain Res. 1994;657:133–40.

    Article  PubMed  Google Scholar 

  42. Ferreira SH, Lorenzetti BB, Bristow AF, Poole S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature. 1998;334:698–700.

    Article  Google Scholar 

  43. Probert L, Plows D, Kontogeorgos G, Kollias G. The type I interleukin-1 receptor acts in series with tumor necrosis factor (TNF) to induce arthritis in TNF-transgenic mice. Eur J Immunol. 1995;25:1794–7.

    Article  PubMed  Google Scholar 

  44. Alstergren P, Kopp S, Theodorsson E. Synovial fluid sampling from the temporomandibular joint: sample quality criteria and levels of interleukin-1 beta and serotonin. Acta Odontol Scand. 1999;57:16–22.

    Article  PubMed  Google Scholar 

  45. Rooney M, Symons JA, Duff GW. Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid arthritis. Rheumatol Int. 1990;10:217–9.

    Article  PubMed  Google Scholar 

  46. Alstergren P, Ernberg M, Kvarnström M, Kopp S. Interleukin-1beta in synovial fluid from the arthritic temporomandibular joint and its relation to pain, mobility, and anterior open bite. J Oral Maxillofac Surg. 1998;56:1059–65.

    Article  PubMed  Google Scholar 

  47. Miller LC, Lynch EA, Isa S, Logan JW, Dinarello CA, Steere AC. Balance of synovial fluid IL-1 beta and IL-1 receptor antagonist and recovery from Lyme arthritis. Lancet. 1993;341:146–8.

    Article  PubMed  Google Scholar 

  48. Matsuda T, Hirano T. IL-6. In: Oppenheim JJ, Feldmann M, Durum SC, Hirano T, Vilcek J, Nicola NA, editors. Cytokine reference. Burlington: Academic; 2000.

    Google Scholar 

  49. Hirano T, Fukada T. IL-6 ligand and receptor family. In: Oppenheim JJ, Feldmann M, Durum SC, Hirano T, Vilcek J, Nicola NA, editors. Cytokine reference. Burlington: Academic; 2000.

    Google Scholar 

  50. Jones SA, Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex. Biochim Biophys Acta. 2002;1592:251–63.

    Article  PubMed  Google Scholar 

  51. Chichorro JG, Lorenzetti BB, Zampronio AR. Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats. Br J Pharmacol. 2004;141:1175–84.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Brenn D, Richter F, Schaible HG. Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical stimuli by interleukin-6 in the rat: an inflammatory mechanism of joint pain. Arthritis Rheum. 2007;56:351–9.

    Article  PubMed  Google Scholar 

  53. Shinoda C, Takaku S. Interleukin-1 beta, interleukin-6, and tissue inhibitor of metalloproteinase-1 in the synovial fluid of the temporomandibular joint with respect to cartilage destruction. Oral Dis. 2000;6:383–90.

    Article  PubMed  Google Scholar 

  54. Kopp S, Alstergren P, Ernestam S, Nordahl S, Morin P, Bratt J. Reduction of temporomandibular joint pain after treatment with a combination of methotrexate and infliximab is associated with changes in synovial fluid and plasma cytokines in rheumatoid arthritis. Cells Tis Org. 2005;180:22–30.

    Article  Google Scholar 

  55. Gyermek L. Pharmacology of serotonin as related to anesthesia. J Clin Anesth. 1996;8:402–25.

    Article  PubMed  Google Scholar 

  56. Richardson BP, Engel G. The pharmacology and function of 5HT3 receptors. Trends Neurosci. 1986;9:424–8.

    Article  Google Scholar 

  57. Birrell GJ, McQueen DS, Iggo A, Grubb BD. The effects of 5-HT on articular sensory receptors in normal and arthritic rats. Br J Pharmacol. 1990;101:715–21.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Alstergren P, Kopp S. Pain and synovial fluid concentration of serotonin in arthritic temporomandibular joints. Pain. 1997;72:137–43.

    Article  PubMed  Google Scholar 

  59. Alstergren P, Fredriksson L, Kopp S. Temporomandibular joint pressure pain threshold is systemically modulated in rheumatoid arthritis. J Orofac Pain. 2008;22(3):231–8.

    PubMed  Google Scholar 

  60. Fredriksson L, Alstergren P, Kopp S. Serotonergic mechanisms influence the response to glucocorticoid treatment in TMJ arthritis. Mediat Inflamm. 2005;2005(4):194–201.

    Article  Google Scholar 

  61. Brooks PM, Day RO. Nonsteroidal anti-inflammatory drugs: differences and similarities. N Engl J Med. 1991;324:1716–25.

    Article  PubMed  Google Scholar 

  62. Levine JD, Taiwo YO. Hyperalgesic pain: a review. Anesth Prog. 1990;37:133–5.

    PubMed  PubMed Central  Google Scholar 

  63. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871–5.

    Article  PubMed  Google Scholar 

  64. Narumiya S, FitzGerald GA. Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest. 2001;108:25–30.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Bhattacharya M, Peri KG, Almazan G, Ribeiro-da-Silva A, Shich H, Durocher Y, Abramovitz M, Hou X, Varma DR, Chemtob S. Nuclear localization of prostaglandin E2 receptors. PNAS. 1998;95:15792–7.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Murakami KI, Shibata T, Kubota E, Maeda H. Intra-artic- ular levels of prostaglandin E2, hyaluronic acid, and chon- droitin-4 and -6 sulfates in the temporomandibular joint synovial fluid of patients with internal derangement. J Oral Maxillofac Surg. 1998;56:199–203.

    Article  PubMed  Google Scholar 

  67. Alstergren P, Kopp S. Prostaglandin E2 in synovial fluid from the arthritic temporomandibular joint and its relation to pain. J Oral Maxillofac Surg. 2000;58:180–6.

    Article  PubMed  Google Scholar 

  68. Lam DK, Sessle BJ, Cairns BE, Hu JW. Neural mechanisms of temporomandibular joint and masticatory muscle pain: a possible role for peripheral glutamate receptor mechanisms. Pain Res Manag. 2005;10:145–52.

    Article  PubMed  Google Scholar 

  69. McNearney T, Baethge BA, Cao S, Alam R, Lisse JR, Westlund KN. Excitatory amino acids, TNF-alpha, and chemokine levels in synovial fluids of patients with active arthropathies. Clin Exp Immunol. 2004;137:621–7.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Alstergren P, Ernberg M, Nilsson M, Hajati AK, Sessle BJ, Kopp S. Glutamate-induced temporomandibular joint pain in healthy individuals is partially mediated by peripheral NMDA receptors. J Orofac Pain. 2010;24(2):172–80.

    PubMed  Google Scholar 

  71. Nash PT, Florin TH. Tumour necrosis factor inhibitors. Med J Australia. 2005;183:205–8.

    PubMed  Google Scholar 

  72. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Therapeutics. 2008;117:244–79.

    Article  Google Scholar 

  73. Maini RN, Taylor PC. Anti-cytokine therapy for rheumatoid arthritis. Ann Rev Med. 2000;51:207–29.

    Article  PubMed  Google Scholar 

  74. Kopp S, Alstergren P, Ernestam S, Nordahl S, Bratt J. Interleukin-1beta influences the effect of infliximab on temporomandibular joint pain in rheumatoid arthritis. Scand J Rheumatol. 2006;35:182–8.

    Article  PubMed  Google Scholar 

  75. Bokarewa M, Tarkowski A. Local infusion of infliximab for the treatment of acute joint inflammation. Ann Rheum Dis. 2003;2:783–4.

    Article  Google Scholar 

  76. Conti F, Priori R, Chimenti MS, Coari G, Annovazzi A, Valesini G, Signore A. Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: a role for scintigraphy with 99mTc-infliximab. Arthritis Rheum. 2005;52:1224–6.

    Article  PubMed  Google Scholar 

  77. Voog U, Alstergren P, Leibur E, Kallikorm R, Kopp S. Influence of serotonin on the analgesic effect of granisetron on temporomandibular joint arthritis. Mediat Inflamm. 2004;13(5–6):373–6.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Per Alstergren DDS, PhD, Med Dr .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag GmbH Germany

About this chapter

Cite this chapter

Alstergren, P. (2017). Molecular Temporomandibular Joint Pain Biomarkers. In: Goulet, JP., Velly, A. (eds) Orofacial Pain Biomarkers. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53994-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-53994-1_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-53992-7

  • Online ISBN: 978-3-662-53994-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics