Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders

Aims: To investigate the relationship between omentin-1 levels and painful temporomandibular disorders (TMD). Methods: In a case-control design, chronic painful TMD cases (n = 90) and TMD-free controls (n = 54) were selected from participants in the multisite OPPERA study (Orofacial Pain: Prospective Evaluation and Risk Assessment). Painful TMD case status was determined by examination using established Research Diagnostic Criteria for TMD (RDC/TMD). Levels of omentin-1 in stored blood plasma samples were measured by using an enzyme-linked immunosorbent assay. Binary logistic regression was used to calculate the odds ratios (ORs) and 95% confidence limits (CLs) for the association between omentin-1 and painful TMD. Models were adjusted for study site, age, sex, and body mass index. Results: The unadjusted association between omentin-1 and chronic painful TMD was statistically nonsignificant (P = .072). Following adjustment for covariates, odds of TMD pain decreased 36% per standard deviation increase in circulating omentin-1 (adjusted OR = 0.64; 95% CL: 0.43, 0.96; P = .031). Conclusion: Circulating levels of omentin-1 were significantly lower in painful TMD cases than controls, suggesting that TMD pain is mediated by inflammatory pathways.

chronic pain; epidemiology; etiology; inflammation mediators; temporomandibular disorders

1. Diatchenko L, Nackley AG, Slade GD, Fillingim RB, Maixner

W. Idiopathic pain disorders--Pathways of vulnerability. Pain 2006;123:226–230.

2. Romero-Reyes M, Uyanik JM. Orofacial pain management: Current perspectives. J Pain Res 2014;7:99–115.

3. Dworkin SF, Huggins KH, LeResche L, et al. Epidemiology of signs and symptoms in temporomandibular disorders: Clinical signs in cases and controls. J Am Dent Assoc 1990; 120:273–281.

4. Isong U, Gansky SA, Plesh O. Temporomandibular joint and muscle disorder-type pain in U.S. adults: The National Health Interview Survey. J Orofac Pain 2008;22:317–322.

5. Carlson CR, Okeson JP, Falace DA, Nitz AJ, Curran SL, Anderson D. Comparison of psychologic and physiologic functioningbetween patients with masticatory muscle pain and matched controls. J Orofac Pain 1993;7:15–22.

6. Maixner W, Diatchenko L, Dubner R, et al. Orofacial pain prospective evaluation and risk assessment study--the OPPERA study. J Pain 2011;12(11, suppl):T4–T11.e1–2.

7. Vassend O, Krogstad BS, Dahl BL. Negative affectivity, somatic complaints, and symptoms of temporomandibular disorders. J Psychosom Res 1995;39:889–899.

8. Slade GD, Fillingim RB, Sanders AE, et al. Summary of findings from the OPPERA prospective cohort study of incidence of first-onset temporomandibular disorder: Implications and future directions. J Pain 2013;14(12, suppl):T116–T124.

9. Slade GD, Conrad MS, Diatchenko L, et al. Cytokine biomarkers and chronic pain: Association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness. Pain 2011;152:2802–2812.

10. Cheng JK, Ji RR. Intracellular signaling in primary sensory neurons and persistent pain. Neurochem Res 2008;33:1970–1978.

11. Copray JC, Mantingh I, Brouwer N, et al. Expression of interleukin-1 beta in rat dorsal root ganglia. J Neuroimmunol 2001; 118:203–211.

12. Sommer C, Häuser W, Gerhold K, et al. Etiology and pathophysiology of fibromyalgia syndrome and chronic widespread pain [article in German]. Schmerz 2008;22:267–282.

13. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin 2007;45:27–37.

14. Kaneyama K, Segami N, Nishimura M, Suzuki T, Sato J. Importance of proinflammatory cytokines in synovial fluid from 121joints with temporomandibular disorders. Br J Oral Maxillofac Surg 2002;40:418–423.

15. Matsumoto K, Honda K, Ohshima M, et al. Cytokine profile in synovial fluid from patients with internal derangement of thetemporomandibular joint: A preliminary study. Dentomaxillofac Radiol 2006;35:432–441.

16. Ogura N, Satoh K, Akutsu M, et al. MCP-1 production in temporomandibular joint inflammation. J Dent Res 2010;89: 1117–1122.

17. 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;85:135–141.

18. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007;132:913–920.

19. Rana SV, Sharma S, Sinha SK, Parsad KK, Malik A, Singh K. Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant irritable bowel syndrome patients. Trop Gastroenterol 2012;33:251–256.

20. Dinan TG, Clarke G, Quigley EM, et al. Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. Am J Gastroenterol 2008;103:2570–2576.

21. Lindenlaub T, Sommer C. Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol 2003;105:593–602.

22. Poole S, Lorenzetti BB, Cunha JM, Cunha FQ, Ferreira SH. Bradykinin B1 and B2 receptors, tumour necrosis factor alpha andinflammatory hyperalgesia. Br J Pharmacol 1999;126: 649–656.

23. Zhang Z, Cherryholmes G, Mao A, et al. High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia. Exp Biol Med (Maywood) 2008;233:1171–1180.

24. Wallace DJ, Linker-Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH. Cytokines play an aetiopathogenetic role in fibromyalgia: A hypothesis and pilot study. Rheumatology (Oxford) 2001;40:743–749.

25. Bazzichi L, Rossi A, Massimetti G, et al. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol 2007;25:225–230.

26. Gür A, Karakoç M, Nas K, et al. Cytokines and depression in cases with fibromyalgia. J Rheumatol 2002;29:358–361.

27. Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: Role in biology. Annu Rev Immunol 1998; 16:27–55.

28. Amel Kashipaz MR, Swinden D, Todd I, Powell RJ. Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clin Exp Immunol 2003;132:360–365.

29. Shibata R, Ouchi N, Kikuchi R, et al. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 2011;219:811–814.

30. Greulich S, Chen WJ, Maxhera B, et al. Cardioprotective prop-erties of omentin-1 in type 2 diabetes: Evidence from clinical and in vitro studies. PLoS One 2013;8:e59697.

31. Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type2 diabetes. Diabetes Res Clin Pract 2010;88:29–33.

32. Senolt L, Polanská M, Filková M, et al. Vaspin and omentin: New adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010;69:1410–1411.

33. Yang RZ, Lee MJ, Hu H, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: Possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006;290:E1253–E1261.

34. de Souza Batista CM, Yang RZ, Lee MJ, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007;56:1655–1661.

35. Bigal ME, Lipton RB. Obesity is a risk factor for transformed migraine but not chronic tension-type headache. Neurology 2006;67:252–257.

36. Delgado-Aros S, Locke GR 3rd, Camilleri M, et al. Obesity is associated with increased risk of gastrointestinal symptoms: A population-based study. Am J Gastroenterol 2004;99:1801–1806.

37. Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF. Obesity and knee osteoarthritis. The Framingham Study. Ann Intern Med 1988;109:18–24.

38. Sanders AE, Slade GD, Bair E, et al. General health status and incidence of first-onset temporomandibular disorder: The OPPERA prospective cohort study. J Pain 2013;14(12, suppl): T51–T62.

39. Dworkin SF. The OPPERA study: Act One. J Pain 2011;12 (11, suppl):T1–T3.

40. Slade GD, Bair E, By K, et al. Study methods, recruitment, sociodemographic findings, and demographic representativenessin the OPPERA study. J Pain 2011;12(11, suppl):T12–T26.

41. Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders: Review, criteria, examinations and specifications, critique. J Craniomandib Disord 1992;6: 301–355.

42. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology2006;130:1480–1491.

43. Wang Q, Feng X, Zhou C, Li P, Kang J. Decreased levels of serum omentin-1 in patients with obstructive sleep apnoea syndrome. Ann Clin Biochem 2013;50(Pt 3):230–235.

44. Ohrbach R, Fillingim RB, Mulkey F, et al. Clinical findings and pain symptoms as potential risk factors for chronic TMD: Descriptive data and empirically identified domains from the OPPERA case-control study. J Pain 2011;12(11, suppl): T27–T45.

45. Gracely RH, McGrath F, Dubner R. Ratio scales of sensory and affective verbal pain descriptors. Pain 1978;5:5–18.

46. Yamawaki H, Kuramoto J, Kameshima S, Usui T, Okada M, Hara

Y. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 2011;408:339–343.

47. Kazama K, Usui T, Okada M, Hara Y, Yamawaki H. Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol 2012;686:116–123.

48. Kim YK, Kim SG, Kim BS, et al. Analysis of the cytokine profiles of the synovial fluid in a normal temporomandibular joint: Preliminary study. J Craniomaxillofac Surg 2012;40:e337–e341.

49. Yin J, Hou P, Wu Z, Nie Y. Decreased levels of serum omentin-1 in patients with inflammatory bowel disease. Med Sci Monit 2015;21:118–122.

50. Li ZG, Zhao DW, Xia CJ, et al. Decreased synovial fluid omentin-1 concentrations reflect symptomatic severity in patients with knee osteoarthritis. Scand J Clin Lab Invest 2012;72:623–628.

51. Furquim BD, Flamengui LM, Conti PC. TMD and chronic pain: A current view. Dental Press J Orthod 2015;20:127–133.