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Interleukin-8 and Matrix Metalloprotease 9 as Salivary Biomarkers of Pain in Patients with Temporomandibular Disorder Myalgia: A Pilot Study

  • Park, Yang Mi (Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital) ;
  • Ahn, Yong-Woo (Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital) ;
  • Jeong, Sung-Hee (Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital) ;
  • Ju, Hye-Min (Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital) ;
  • Jeon, Hye-Mi (Department of Oral Medicine, Pusan National University Hospital) ;
  • Kim, Kyung-Hee (Department of Oral Medicine, Inje University Busan Paik Hospital) ;
  • Ok, Soo-Min (Department of Oral Medicine, Dental Research Institute, Pusan National University Dental Hospital)
  • Received : 2019.11.25
  • Accepted : 2019.12.20
  • Published : 2019.12.30

Abstract

Purpose: To search the salivary factors that objectively indicate an pain in myalgia patients with temporomandibular joint disorder (TMD) and determine the possibility of the factors as pain-biomarkers. Methods: Participants consisted of pain-free 15 persons (male 7, female 8, mean age±standard deviation (SD); 26.8±16.04 years) and 45 myalgia patients with TMD (male 21, female 24, mean age±SD; 27.98±13.01 years). They were divided into a pain-free group (numerical rating scale [NRS] score 0), a mild pain group (NRS 1-4), a moderate pain group (NRS 5-6), and a severe pain group (NRS 7-10) and members of all groups were age, sex matched. Interleukin-8 (IL-8) and matrix metalloprotease 9 (MMP-9) were selected as pain biomarkers, by searching the Gene Expression Omnibus database and analyzing pain-related genes. Enzyme-linked immunosorbent assays were used to measure the concentration of IL-8 and MMP-9 in the patients' saliva. Results: IL-8 and MMP-9 levels were statistically significantly higher in pain groups than in the pain-free group. Greater differences were observed in patients with acute pain (with painful duration under 3 months) than in the control group and in female patients than in male. Conclusions: Salivary IL-8 and MMP-9 may play a role as biomarkers of myalgia in patients with TMD.

Keywords

References

  1. Montes-Sandoval L. An analysis of the concept of pain. J Adv Nurs 1999;29:935-941. https://doi.org/10.1046/j.1365-2648.1999.00971.x
  2. Shibata M, Kawai M, Matsukura T, Heike T, Okanoya K, Myowa-Yamakoshi M. Salivary biomarkers are not suitable for pain assessment in newborns. Early Hum Dev 2013;89:503-506. https://doi.org/10.1016/j.earlhumdev.2013.03.006
  3. Sobas EM, Reinoso R, Cuadrado-Asensio R, Fernandez I, Maldonado MJ, Pastor JC. Reliability of potential pain biomarkers in the saliva of healthy subjects: inter-individual differences and intersession variability. PLoS One 2016;11:e0166976. https://doi.org/10.1371/journal.pone.0166976
  4. Von Korff M, Jensen MP, Karoly P. Assessing global pain severity by self-report in clinical and health services research. Spine (Phila Pa 1976) 2000;25:3140-3151. https://doi.org/10.1097/00007632-200012150-00009
  5. Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs 2005;14:798-804. https://doi.org/10.1111/j.1365-2702.2005.01121.x
  6. Hjermstad MJ, Fayers PM, Haugen DF, et al. Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011;41:1073-1093. https://doi.org/10.1016/j.jpainsymman.2010.08.016
  7. Conti PC, Costa YM, Goncalves DA, Svensson P. Headaches and myofascial temporomandibular disorders: overlapping entities, separate managements? J Oral Rehabil 2016;43:702-715. https://doi.org/10.1111/joor.12410
  8. Cairns BE. Pathophysiology of TMD pain--basic mechanisms and their implications for pharmacotherapy. J Oral Rehabil 2010;37:391-410. https://doi.org/10.1111/j.1365-2842.2010.02074.x
  9. Javaid MA, Ahmed AS, Durand R, Tran SD. Saliva as a diagnostic tool for oral and systemic diseases. J Oral Biol Craniofac Res 2016;6:66-75.
  10. Nunes LA, Mussavira S, Bindhu OS. Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid: a systematic review. Biochem Med (Zagreb) 2015;25:177-192. https://doi.org/10.11613/BM.2015.018
  11. Balan JJ, Rao RS, Premalatha BR, Patil S. Analysis of tumor marker CA 125 in saliva of normal and oral squamous cell carcinoma patients: a comparative study. J Contemp Dent Pract 2012;13:671-675. https://doi.org/10.5005/jp-journals-10024-1207
  12. Floriano PN, Christodoulides N, Miller CS, et al. Use of salivabased nano-biochip tests for acute myocardial infarction at the point of care: a feasibility study. Clin Chem 2009;55:1530-1538. https://doi.org/10.1373/clinchem.2008.117713
  13. Smith SM, Dworkin RH, Turk DC, et al. The potential role of sensory testing, skin biopsy, and functional brain imaging as biomarkers in chronic pain clinical trials: IMMPACT considerations. J Pain 2017;18:757-777. https://doi.org/10.1016/j.jpain.2017.02.429
  14. Jin EH, Zhang E, Ko Y, et al. Genome-wide expression profiling of complex regional pain syndrome. PLoS One 2013;8:e79435. https://doi.org/10.1371/journal.pone.0079435
  15. Treede RD, Rief W, Barke A, et al. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain 2019;160:19-27. https://doi.org/10.1097/j.pain.0000000000001384
  16. Shahzad A, Knapp M, Lang I, Kohler G. Interleukin 8 (IL-8)-a universal biomarker? Int Arch Med 2010;3:11. https://doi.org/10.1186/1755-7682-3-11
  17. Ahn SH, Cho YW, Ahn MW, Jang SH, Sohn YK, Kim HS. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine (Phila Pa 1976) 2002;27:911-917. https://doi.org/10.1097/00007632-200205010-00005
  18. Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br 2002;84:196-201. https://doi.org/10.1302/0301-620X.84B2.0840196
  19. Ang DC, Moore MN, Hilligoss J, Tabbey R. MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study. Pain Med 2011;12:1154-1161. https://doi.org/10.1111/j.1526-4637.2011.01179.x
  20. Wang H, Moser M, Schiltenwolf M, Buchner M. Circulating cytokine levels compared to pain in patients with fibromyalgia- a prospective longitudinal study over 6 months. J Rheumatol 2008;35:1366-1370.
  21. White AT, Light AR, Hughen RW, et al. Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome. Psychophysiology 2010;47:615-624. https://doi.org/10.1111/j.1469-8986.2010.00978.x
  22. 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. https://doi.org/10.1016/j.pain.2011.09.005
  23. Louca Jounger S, Christidis N, Svensson P, List T, Ernberg M. Increased levels of intramuscular cytokines in patients with jaw muscle pain. J Headache Pain 2017;18:30. https://doi.org/10.1186/s10194-017-0737-y
  24. Ribeiro RA, Vale ML, Thomazzi SM, et al. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur J Pharmacol 2000;387:111-118. https://doi.org/10.1016/S0014-2999(99)00790-6
  25. Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ. Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 2001;21:5027-5035. https://doi.org/10.1523/jneurosci.21-14-05027.2001
  26. Cruz-Almeida Y, Aguirre M, Sorenson HL, Tighe P, Wallet SM, Riley JL 3rd. Age differences in cytokine expression under conditions of health using experimental pain models. Exp Gerontol 2015;72:150-156. https://doi.org/10.1016/j.exger.2015.09.017
  27. Reyes-Gibby CC, Wang J, Spitz M, Wu X, Yennurajalingam S, Shete S. Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients. J Pain Symptom Manage 2013;46:161-172. https://doi.org/10.1016/j.jpainsymman.2012.07.019
  28. Reyes-Gibby CC, Spitz M, Wu X, et al. Cytokine genes and pain severity in lung cancer: exploring the influence of TNFalpha-308 G/A IL6-174G/C and IL8-251T/A. Cancer Epidemiol Biomarkers Prev 2007;16:2745-2751. https://doi.org/10.1158/1055-9965.EPI-07-0651
  29. Reyes-Gibby CC, Shete S, Yennurajalingam S, et al. Genetic and nongenetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes. J Pain Symptom Manage 2009;38:894-902. https://doi.org/10.1016/j.jpainsymman.2009.04.019
  30. Vafadari B, Salamian A, Kaczmarek L. MMP-9 in translation: from molecule to brain physiology, pathology, and therapy. J Neurochem 2016;139(Suppl 2):91-114. https://doi.org/10.1111/jnc.13415
  31. Lakhan SE, Avramut M. Matrix metalloproteinases in neuropathic pain and migraine: friends, enemies, and therapeutic targets. Pain Res Treat 2012;2012:952906. https://doi.org/10.1155/2012/952906
  32. Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache 2008;48:135-139. https://doi.org/10.1111/j.1526-4610.2007.00958.x
  33. Martinho FC, Teixeira FF, Cardoso FG, et al. Clinical investigation of matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase complexes and their networks in apical periodontitis. J Endod 2016;42:1082-1088. https://doi.org/10.1016/j.joen.2016.04.001
  34. Dagher A, Curatolo A, Sachdev M, et al. Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int 2017;120:130-142. https://doi.org/10.1111/bju.13832
  35. Salmos-Brito JA, de Menezes RF, Teixeira CE, et al. Evaluation of low-level laser therapy in patients with acute and chronic temporomandibular disorders. Lasers Med Sci 2013;28:57-64. https://doi.org/10.1007/s10103-012-1065-8
  36. Greenspan JD, Slade GD, Bair E, et al. Pain sensitivity risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case control study. J Pain 2011;12(11 Suppl):T61-T74. https://doi.org/10.1016/j.jpain.2011.08.006
  37. Slade GD, Sanders AE, Ohrbach R, et al. Pressure pain thresholds fluctuate with, but do not usefully predict, the clinical course of painful temporomandibular disorder. Pain 2014;155:2134-2143. https://doi.org/10.1016/j.pain.2014.08.007
  38. Sessle BJ. The neural basis of temporomandibular joint and masticatory muscle pain. J Orofac Pain 1999;13:238-245.
  39. Kimos P, Biggs C, Mah J, et al. Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial. Pain 2007;127:151-160. https://doi.org/10.1016/j.pain.2006.08.028
  40. Grosman-Rimon L, Kumbhare DA. Inflammatory biomarkers in acute myofascial pain. PM R 2016;8(9S):S155. https://doi.org/10.1016/j.pmrj.2016.07.029
  41. Grosman-Rimon L, Parkinson W, Upadhye S, et al. Circulating biomarkers in acute myofascial pain: a case-control study. Medicine (Baltimore) 2016;95:e4650. https://doi.org/10.1097/md.0000000000004650
  42. Backryd E. Pain in the blood? Envisioning mechanism-based diagnoses and biomarkers in clinical pain medicine. Diagnostics (Basel) 2015;5:84-95. https://doi.org/10.3390/diagnostics5010084
  43. van de Vyver M, Engelbrecht L, Smith C, Myburgh KH. Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL-6, IL-10, pstat3, and SOCS3. Scand J Med Sci Sports 2016;26:638-647. https://doi.org/10.1111/sms.12497
  44. Andersson M, Ruber M, Ekerfelt C, Hallgren HB, Olaison G, Andersson RE. Can new inflammatory markers improve the diagnosis of acute appendicitis? World J Surg 2014;38:2777-2783. https://doi.org/10.1007/s00268-014-2708-7
  45. Ghurye S, McMillan R. Pain-related temporomandibular disorder - current perspectives and evidence-based management. Dent Update 2015;42:533-536, 539-542, 545-546. https://doi.org/10.12968/denu.2015.42.6.533
  46. Bueno CH, Pereira DD, Pattussi MP, Grossi PK, Grossi ML. Gender differences in temporomandibular disorders in adult populational studies: a systematic review and meta-analysis. J Oral Rehabil 2018;45:720-729. https://doi.org/10.1111/joor.12661
  47. Ribeiro-Dasilva MC, Fillingim RB, Wallet SM. Estrogen-induced monocytic response correlates with TMD pain: a case control study. J Dent Res 2017;96:285-291. https://doi.org/10.1177/0022034516678599
  48. Abrahamsen R, Zachariae R, Svensson P. Effect of hypnosis on oral function and psychological factors in temporomandibular disorders patients. J Oral Rehabil 2009;36:556-570. https://doi.org/10.1111/j.1365-2842.2009.01974.x
  49. Anna S, Joanna K, Teresa S, Maria G, Aneta W. The influence of emotional state on the masticatory muscles function in the group of young healthy adults. Biomed Res Int 2015;2015:174013. https://doi.org/10.1155/2015/174013
  50. Flake NM, Bonebreak DB, Gold MS. Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. J Neurophysiol 2005;93:1585-1597. https://doi.org/10.1152/jn.00269.2004