Salivary Levels of Interleukin-1𝛃 in Temporomandibular Disorders and Fibromyalgia

Aims: To evaluate salivary levels of the proinflammatory cytokine interleukin-1β (IL-1β) in patients with temporomandibular disorders (TMD), fibromyalgia, or both conditions in comparison to healthy individuals. Methods: A total of 69 females (18 to 84 years of age) were assigned to one of four groups: (A) healthy controls (n = 27); (B) TMD only (n = 18); (C) fibromyalgia only (n = 15); and (D) fibromyalgia plus TMD (n = 9). Clinical data and salivary IL-1β levels were evaluated. Statistical analysis was performed by using Fischer exact test, unpaired Student t test, or one-way analysis of variance plus multiple comparisons Tukey test, depending on the variable. The correlation between age and IL-1β levels was assessed by using Pearson correlation coefficient. Results: Most patients in groups B and D displayed clinical features of Group I (muscle disorders) and Group II (disc displacements) of the Axis I Research Diagnostic Criteria for Temporomandibular Disorders. The subjects in groups C and D presented values of > 7 on the Widespread Pain Index (WPI) and > 5 for Symptom Severity Score (SS) according to the Fibromyalgia Survey Diagnostic Criteria and Severity Scale. There were no significant differences when SS and WPI levels were compared between groups C and D. The patients with TMD showed significantly higher salivary IL-1β levels irrespective of a fibromyalgia diagnosis (groups B and D), whereas the fibromyalgia-only patients (group C) did not show any significant difference in relation to controls. Conclusion: This study provides novel evidence indicating that salivary IL-1β may be a biomarker for TMD.

fibromyalgia;IL-1β;patients;saliva;temporomandibular disorders

1.Mease P, Arnold LM, Bennett R, et al. Fibromyalgia syndrome. J Rheumatol 2007;34:1415–1425.

2.Walters A, Tolle SL, McCombs GM. Fibromyalgia syn-drome: Considerations for dental hygienists. J Dent Hyg 2015;89:76–85.

3.Sommer I, Lavigne G, Ettlin DA. Review of self-reported in-struments that measure sleep dysfunction in patients suffer-ing from temporomandibular disorders and/or orofacial pain. Sleep Med 2015;16:27–38.

4.Ahmad M, Schiffman EL. Temporomandibular joint disorders and orofacial pain. Dent Clin North Am 2016;60:105–124.

5.Robinson LJ, Durham J, Newton JL. A systematic review of the comorbidity between temporomandibular disorders and chronic fatigue syndrome. J Oral Rehabil 2016;43:306–316.

6.Shaffer SM, Brismée JM, Sizer PS, Courtney CA. Temporomandibular disorders. Part 1: Anatomy and examina-tion/diagnosis. J Man Manip Ther 2014;22:2–12.

7.Yule PL, Durham J, Wassell RW. Pain part 6: Temporo-mandibular disorders. Dent Update 2016;43:39–48.

8.Dahan H, Shir Y, Velly A, Allison P. Specific and number of comorbidities are associated with increased levels of tem-poromandibular pain intensity and duration. J Headache Pain 2015;16:528.

9.Dahan H, Shir Y, Nicolau B, Keith D, Allison P. Self-reported migraine and chronic fatigue syndrome are more prevalent in people with myofascial vs nonmyofascial temporomandibular disorders. J Oral Facial Pain Headache 2016;30:7–13.

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

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

12.Nishimura M, Segami N, Kaneyama K, Sato J, Fujimura K. Comparison of cytokine level in synovial fluid between success-ful and unsuccessful cases in arthrocentesis of the temporo-mandibular joint. J Oral Maxillofac Surg 2004;62:284–287.

13.Gulen H, Ataoglu H, Haliloglu S, Isik K. Proinflammatory cyto-kines in temporomandibular joint synovial fluid before and after arthrocentesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:e1–e4.

14.Park JW, Chung JW. Inflammatory cytokines and sleep distur-bance in patients with temporomandibular disorders. J Oral Facial Pain Headache 2016;30:27–33.

15.Kellesarian SV, Al-Kheraif AA, Vohra F, et al. Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review. Cytokine 2016;77:98–106.

16.Uçeyler N, Häuser W, Sommer C. Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome. BMC Musculoskelet Disord 2011;12:245.

17.Rodriguez-Pintó I, Agmon-Levin N, Howard A, Shoenfeld Y. Fibromyalgia and cytokines. Immunol Lett 2014;161:200–203.

18.Sturgill J, McGee E, Menzies V. Unique cytokine signature in the plasma of patients with fibromyalgia. J Immunol Res 2014; 2014:938576.

19.Tsilioni I, Russell IJ, Stewart JM, Gleason RM, Theoharides TC. Neuropeptides CRH, SP, HK-1, and inflammatory cytokines IL-6 and TNF are increased in serum of patients with fibromy-algia syndrome, implicating mast cells. J Pharmacol Exp Ther 2016;356:664–672.

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

21.García-Lozano JR, Capilla-Sevilla C, García-López O, Moreno-Gallego I. Correlation between cytokines and anxious-depressive symptoms in patients with fibromyalgia. Reumatol Clin 2008;4:136–139.

22.Nakamura T, Schwander SK, Donnelly R, et al. Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia. Clin Vaccine Immunol 2010;17:582–587.

23.Dell’Osso L, Bazzichi L, Baroni S, et al. The inflammato-ry hypothesis of mood spectrum broadened to fibromy-algia and chronic fatigue syndrome. Clin Exp Rheumatol 2015;33(suppl):s109–s116.

24.Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E. Evidence of central inflammation in fibromyalgia increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol 2012;242:33–38.

25.Üçeyler N, Kewenig S, Kafke W, Kittel-Schneider S, SommerC. Skin cytokine expression in patients with fibromyalgia syn-drome is not different from controls. BMC Neurol 2014;14:185.

26. Christidis N, Ghafouri B, Larsson A, et al. Comparison of the levels of pro-inflammatory cytokines released in the vastus lat-eralis muscle of patients with fibromyalgia and healthy controls during contractions of the quadriceps muscle—A microdialysis study. PLoS One 2015;10:e0143856.

27.Schiffman E, Ohrbach R. Executive summary of the Diagnostic Criteria for Temporomandibular Disorders for clinical and re-search applications. J Am Dent Assoc 2016;147:438–445.

28.Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 2011;38:1113–1122.

29.Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62:600–610.

30.Hoffmann RR, Yurgel LS, Campos MM. Evaluation of salivary endothelin-1 levels in oral squamous cell carcinoma and oral leukoplakia. Regul Pept 2011;166:55–58.

31.Yunus MB. The role of gender in fibromyalgia syndrome. Curr Rheumatol Rep 2001;3:128–134.

32.Yunus MB. Gender differences in fibromyalgia and other relat-ed syndromes. J Gend Specif Med 2002;5:42–47.

33.Hoffmann RG, Kotchen JM, Kotchen TA, Cowley T, Dasgupta M, Cowley AW Jr. Temporomandibular disorders and associat-ed clinical comorbidities. Clin J Pain 2011;27:268–274.

34.Arnold LM, Choy E, Clauw DJ, et al. Fibromyalgia and chronic pain syndromes: A white paper detailing current challenges in the field. Clin J Pain 2016;32:737–746.

35.Janal MN, Raphael KG, Cook DB, Sirois DA, Nemelivsky L, Staud R. Thermal temporal summation and decay of after-sensations in temporomandibular myofascial pain patients with and without comorbid fibromyalgia. J Pain Res 2016;9:641–652.

36.Fraga BP, Santos EB, Farias Neto JP, et al. Signs and symp-toms of temporomandibular dysfunction in fibromyalgic pa-tients. J Craniofac Surg 2012;23:615–618.

37. Yunus MB. The prevalence of fibromyalgia in other chronic pain conditions. Pain Res Treat 2012;2012:584573.

38.Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 2017;76:318–328.

39.Verri WA Jr, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH. Hypernociceptive role of cytokines and chemok-ines: Targets for analgesic drug development? Pharmacol Ther 2006;112:116–138.

40.Walker AK, Kavelaars A, Heijnen CJ, Dantzer R. Neuroinflammation and comorbidity of pain and depression. Pharmacol Rev 2013;66:80–101.

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

42.Woda A, Picard P, Dutheil F. Dysfunctional stress responses in chronic pain. Psychoneuroendocrinology 2016;71:127–135.

43.Teles RP, Likhari V, Socransky SS, Haffajee AD. Salivary cy-tokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: A cross-sectional study. J Periodontal Res 2009;44:411–417.

44.Nie S, Zhang H, Mayer KM, et al. Correlations of salivary bio-markers with clinical assessments in patients with cystic fibro-sis. PLoS One 2015;10:e0135237.

45.Wormwood KL, Aslebagh R, Channaveerappa D, et al. Salivary proteomics and biomarkers in neurology and psychia-try. Proteomics Clin Appl 2015;9:899–906.

46.Da Silva Andrade A, Gamero GH, Pereira LJ, Junqueira Zanin IC, Gavião MB. Salivary cortisol levels in young adults with tem-poromandibular disorders. Minerva Stomatol 2008;57:109–116.

47.Quartana PJ, Buenaver LF, Edwards RR, Klick B, Haythornthwaite JA, Smith MT. Pain catastrophizing and sali-vary cortisol responses to laboratory pain testing in temporo-mandibular disorder and healthy participants. J Pain 2010;11: 186–194.

48.Riva R, Mork PJ, Westgaard RH, Lundberg U. Comparison of the cortisol awakening response in women with shoulder and neck pain and women with fibromyalgia. Psychoneuroendocrinology 2012;37:299–306.

49.Wingenfeld K, Nutzinger D, Kauth J, Hellhammer DH, Lautenbacher S. Salivary cortisol release and hypothalam-ic pituitary adrenal axis feedback sensitivity in fibromyalgia is associated with depression but not with pain. J Pain 2010; 11:1195–1202.