Orofacial Pain and Toothache as the Sole Symptom of an Acute Myocardial Infarction Entails a Major Risk of Misdiagnosisand Death

Aims: To provide an update of knowledge regarding the clinical presentation and neurophysiologic aspects of orofacial pain of cardiac origin in the form of a literature review. Methods: The peer-reviewed databases Scopus/Embase, NCBI (PubMed), and Science Direct were searched up to December 2018. Results: Patients with myocardial infarction presenting without chest pain run a higher risk of death due to missed diagnosis and subsequently a significantly greater delay between the onset of symptoms and arrival at the hospital. During myocardial ischemia, orofacial pain is reported by 4 in 10 patients and described as oppressive and/or burning. Up to 4% of myocardial infarction patients experience pain solely in the orofacial structures, women more often than men. Orofacial pain during myocardial ischemia is associated with ischemia within the inferior wall of the heart, suggesting the involvement of the vagal system. Conclusion: The clinician’s awareness of the full spectrum of clinical characteristics of a myocardial infarction constitutes a key factor in accurate diagnosis. Health care professionals and the general public should be aware of the possibility of myocardial infarction presenting with orofacial pain, toothache, or ear/temporomandibular joint pain as the only symptom.

cardiac ischemia; cardiac pain; myocardial infarction; orofacial pain; toothache

1. McCarthy BD, Beshansky JR, D’Agostino RB, Sekler HP. Missed diagnoses of acute myocardial infarction in the emergency department: Results from a multicenter study. Ann Emerg Med 1993;22:579–582.

2. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342:1163–1170.

3. Sebbane M, Lefebvre S, Kuster N, et al. Early rule out of acute myocardial infarction in ED patients: Value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission. Am J Emerg Med 2013;31:1302–1308.

4. Mesas CE, Rodrigues RJ, Mesas AE, et al. Symptoms awareness, emergency medical service utilization and hospital transfer delay in myocardial infarction. BMC Health Serv Res 2018;18:490.

5. Fesmire FM, Wears RL. The utility of the presence or absence of chest pain in patients with suspected acute myocardial infarction. Am J Emerg Med 1989;7:372–377.

6. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000; 283:3223–3229.

7. Gao Y, Zhang HJ. The effect of symptoms on prehospital delay time in patients with acute myocardial infarction. J Int Med Res 2013;41:1724–1731.

8. Nielsen CG, Laut KG, Jensen LO, Ravkilde J, Terkelsen CJ, Kristensen SD. Patient delay in patients with ST-elevation myocardial infarction: Time patterns and predictors for a prolonged delay. Eur Heart J Acute Cardiovasc Care 2017;6:583–591.

9. Then KL, Rankin JA, Fofonoff DA. Atypical presentation of acute myocardial infarction in 3 age groups. Heart Lung 2001;30:285–293.

10. Kreiner M, Okeson JP, Michelis V, Lujambio M, Isberg A. Craniofacial pain as the sole symptom of cardiac ischemia: A prospective multicenter study. J Am Dent Assoc 2007; 138:74–79.

11. Danesh-Sani SH, Danesh-Sani SA, Zia R, Faghihi S. Incidence of craniofacial pain of cardiac origin: Results from a prospective multicentre study. Aust Dent J 2012;57:355–358.

12. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction. J Am Coll Cardiol 2007;50:e1–e157.

13. Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525–2538.

14. Cannon CP, Battler A, Brindis RG, et al. American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes. A report of the American College of Cardiology Task Force on Clinical Data standards (Acute Coronary Syndromes Writing Committee). J Am Coll Cardiol 2001;38:2114–2130.

15. Luepker RV, Apple FS, Christenson RH, et al. Case definitions for acute coronary heart disease in epidemiology and clinicalresearch studies: A statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003;108:2543–2549.

16. Fox KA, Birkhead J, Wilcox R, Knight C, Barth J, British Cardiac Society Working Group. British Cardiac Society Working Group on the definition of myocardial infarction. Heart 2004;90:603–609.

17. Biagini A, Emdin M, Mazzei MG, et al. Clinical characteristics of anginal pain in man. Funct Neurol 1989;4:43–45.

18. Eriksson B, Vuorisalo D, Sylvén C. Diagnostic potential of chest pain characteristics in coronary care. J Intern Med 1994; 235:473–478.

19. Zerwic JJ. Symptoms of acute myocardial infarction: Expectations of a community sample. Heart Lung 1998;27: 75–81.

20. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guide-lines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004;44:E1–E211.

21. Herlitz J, Karlson BW, Richter A, Strömbom U, Hjalmarson A. Prognosis for patients with initially suspected acute myocardial infarction in relation to presence of chest pain. Clin Cardiol 1992;15:570–576.

22. Dorsch MF, Lawrance RA, Sapsford RJ, et al. Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain. Heart 2001;86:494–498.

23. Brieger D, Eagle KA, Goodman SG, et al. Acute coronary syndromes without chest pain, an underdiagnosed and undertreated high-risk group: Insights from the global registry of acute coronary events. Chest 2004;126:461–469.

24. Uretsky BF, Farquhar DS, Berezin AF, Hood WB Jr. Symptomatic myocardial infarction without chest pain: Prevalence and clinical course. Am J Cardiol 1977;40:498–503.

25. Zdzienicka J, Siudak Z, Zawis´lak B, et al. Patients with non-ST-elevation myocardial infarction and without chest pain are treated less aggressively and experience higher in-hospital mortality. Kardiol Pol 2007;65:769–775.

26. Goldstein RE, Boccuzzi SJ, Cruess D. Prognosis after hospitalization for acute myocardial infarction not accompanied by typical ischemic chest pain. The Multicenter Diltiazem Post-infarction Trial Research Group. Am J Med 1995;99:123–131.

27. Tzukert A, Hasin Y, Sharav Y. Orofacial pain of cardiac origin. Oral Surg Oral Med Oral Pathol 1981;51:484–486.

28. Batchelder BJ, Krutchkoff DJ, Amara J. Mandibular pain as the initial and sole clinical manifestation of coronary insufficiency: Report of case. J Am Dent Assoc 1987;115:710–712.

29. Peñarrocha Diago M, Silvestre Donat FJ, Rodriguez Gil R. Facial pain of cardiac origin [in French]. Rev Stomatol Chir Maxillofac 1990;91:477–479.

30. Takayanagi K, Fujito T, Morooka S, Takabatake Y, Nakamura Y. Headache angina with fatal outcome. Jpn Heart J 1990;31: 503–507.

31. Rothwell PM. Angina and myocardial infarction presenting with pain confined to the ear. Postgrad Med J 1993;69:300–301.

32. Ishida A, Sunagawa O, Touma T, Shinazato Y, Kawazoe N, Fukiyama K. Headache as a manifestation of myocardial infarction. Jpn Heart J 1996;37:261–263.

33. Grace A, Horgan J, Breatnach K, Staunton H. Anginal head-ache and its basis. Cephalalgia 1997;17:195–196.

34. Kreiner M, Okeson JP. Toothache from cardiac origin. J Orofac Pain 1999;13:201–207.

35. Dalband M, Mortazavi H, Hashem-Zehi H. Bilateral temporomandibular joint pain as the first and only symptom of ischemic cardiac disease: A case report. Chang Gung Med J 2011: 34(6, suppl):s1–s3.

36. Adachi M, Hayashi M, Segawa T, Yamaki T, Muramatsu Y, Sumitomo S. Orofacial pain associated with vasospastic angina: A case report. J Oral Facial Pain Headache 2017;31:e1–e3.

37. Kreiner M, Falace D, Michelis V, Okeson JP, Isberg A. Quality difference in craniofacial pain of cardiac vs. dental origin. J Dent Res 2010;89:965–969.

38. Kreiner M, Alvarez R, Waldenström A. Michelis V, Muñiz R, Isberg A. Craniofacial pain of cardiac origin is associated with inferior wall ischemia. J Oral Facial Pain Headache 2014;28:317–321.

39. Kreiner M, Álvarez R, Michelis V, Waldenström A, Isberg A. Craniofacial pain can be the sole prodromal symptom of an acute myocardial infarction: An interdisciplinary study. Acta Odontol Latinoam 2016;29:23–28.

40. Danesh-Sani SH, Danesh-Sani SA, Zia R, Faghihi S. Incidence of craniofacial pain of cardiac origin: Results from a prospective multicentre study. Aust Dent J 2012;57:355–358.

41. Bakhshi M, Rezaei R, Baharvand M, Bakhtiari S. Frequency of craniofacial pain in patients with ischemic heart disease. J Clin Exp Dent 2017;9:e91–e95.

42. Henry MA, Hargreaves KM. Peripheral mechanisms of odontogenic pain. Dent Clin North Am 2007;51:19–44.

43. Johansson AS, Isacsson G, Isberg A, Granholm AC. Distribution of substance P-like immunoreactive nerve fibers in temporomandibular joint soft tissues of monkey. Scand J Dent Res 1986;94:225–232.

44. Kopp S. The influence of neuropeptides, serotonin, and interleukin 1beta on temporomandibular joint pain and inflammation. J Oral Maxillofac Surg 1998;56:189–191.

45. Sessle BJ. New insights into peripheral chemical mediators of temporomandibular pain and inflammation. J Orofac Pain 2001; 15:5.

46. Sessle BJ. Peripheral and central mechanisms of orofacial pain and their clinical correlates. Minerva Anestesiol 2005;71:117–136.

47. Park CK, Bae JH, Kim HY, et al. Substance P sensitizes P2X3 in nociceptive trigeminal neurons. J Dent Res 2010;89: 1154–1159.

48. Villa G, Ceruti S, Zanardelli M, et al. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus. Mol Pain 2010;6:89.

49. Watanabe M, Shinoda M, Batbold D, Sugano N, Sato S, Iwata K. Peripheral glial cell line-derived neurotrophic factor facilitates the functional recovery of mechanical nociception following inferior alveolar nerve transection in rats. J Oral Facial Pain Headache 2018;32:229–237.

50. Sessle BJ. Acute and chronic craniofacial pain: Brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 2000;11:57–91.

51. Li JL, Xiong KH, Dong YL, Fujiyama F, Kaneko T, Mizuno N. Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression. J Comp Neurol 2003;463:212–220.

52. Hegarty DM, Tonsfeldt K, Hermes SM, Helfand H, Aicher SA. Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis. J Comp Neurol 2010;518:3557–3569.

53. Avendaño C, Machín R, Bermejo PE, Lagares A. Neuron numbers in the sensory trigeminal nuclei of the rat: A GABA- and glycineimmunocytochemical and stereological analysis. J Comp Neurol 2005;493:538–553.

54. Bae YC, Park KS, Bae JY, et al. GABA and glycine in synaptic microcircuits associated with physiologically characterized primary afferents of cat trigeminal principal nucleus. Exp Brain Res 2005;162:449–457.

55. Martin YB, Malmierca E, Avendaño C, Nuñez A. Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic pain. Eur J Neurosci 2010;32:399–408.

56. Kim MJ, Park YH, Yang KY, et al. Participation of central GABAA receptors in the trigeminal processing of mechanical allodynia in rats. Korean J Physiol Pharmacol 2017;21:65–74.

57. Lechner J, Leah JD, Zimmermann M. Brainstem peptidergic neurons projecting to the medial and lateral thalamus and zona incerta in the rat. Brain Res 1993;603:47–56.

58. Guy N, Chalus M, Dallel R, Voisin DL. Both oral and caudal parts of the spinal trigeminal nucleus project to the somatosensory thalamus in the rat. Eur J Neurosci 2005; 21:741–754.

59. Thorén PN. Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol 1976;37:1046–1051.

60. Hashimoto K, Hirose M, Furukawa S, Hayakawa H, Kimura E. Changes in hemodynamics and bradykinin concentration in coronary sinus blood in experimental coronary artery occlu-sion. Jpn Heart J 1977;18:679–689.

61. Fredholm BB, Sollevi A. Cardiovascular effects of adenosine. Clin Physiol 1986;6:1–21.

62. Edlund A, Fredholm BB, Patrignani P, Patrono C, Wennmalm A, Wennmalm M. Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia. J Physiol 1983;340:487–501.

63. Fu LW, Schunack W, Longhurst JC. Histamine contributes to ischemia-related activation of cardiac spinal afferents: Role of H1 receptors and PKC. J Neurophysiol 2005;93:713–722.

64. Fu LW, Longhurst JC. Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia. Am J Physiol Heart Circ Physiol 2010;298:H235–H244.

65. Blair RW, Weber RN, Foreman RD. Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey. Circ Res 1982;51:83–94.

66. Qin C, Du JQ, Tang JS, Foreman RD. Bradykinin is involved in the mediation of cardiac nociception during ischemia through upper thoracic spinal neurons. Curr Neurovasc Res 2009; 6:89–94.

67. Kawano H, Okada R, Yano K. Histological study on the distribution of autonomic nerves in the human heart. Heart Vessels 2003;18:32–39.

68. Foreman RD, Qin C. Neuromodulation of cardiac pain and cerebral vasculature: Neural mechanisms. Cleve Clin J Med 2009; 76(suppl):s75–s79.

69. Chandler MJ, Zhang J, Foreman RD. Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys. J Neurophysiol 1996;76:2555–2567.

70. Foreman RD. Mechanisms of cardiac pain. Ann Rev Physiol 1999;61:143–167.

71. Qin C, Chandler MJ, Miller KE, Foreman RD. Responses and afferent pathways of superficial and deeper c(1)–c(2) spinal cells to intrapericardial algogenic chemicals in rats. J Neurophysiol 2001;85:1522–1532.

72. Kuo DC, Oravitz JJ, DeGroat WC. Tracing of afferent and efferent pathways in the left inferior cardiac nerve of the cat using retrograde and transport of horseradish peroxidase. Brain Res 1984;321:111–118.

73. McNeill DL, Chandler MJ, Fu QG, Foreman RD. Projection of nodose ganglion cells to the upper cervical spinal cord in the rat. Brain Res Bull 1991;27:151–155.

74. Chandler MJ, Qin C, Yuan Y, Foreman RD. Convergence of trigeminal input with visceral and phrenic inputs on primate C1–C2 spinothalamic tract neurons. Brain Res 1999;829: 204–208.

75. Sessle BJ, Hu JW, Amano N, Zhong G. Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain1986;27:219–235.

76. Bossut DF, Maixner W. Effects of cardiac vagal afferent electrostimulation on the responses of trigeminal and trigeminothalamic neurons to noxious orofacial stimulation. Pain 1996; 65:101–109.

77. Foreman RD. Neurological mechanisms of chest pain and cardiac disease. Cleve Clin J Med 2007;74(suppl 1):s30–s33.

78. Ansari S, Chaudhri K, Al Moutaery KA. Vagus nerve stimulation: Indications and limitations. Acta Neurochir Suppl 2007; 97:281–286.

79. Myers DE. Vagus nerve pain referred to the craniofacial region. A case report and literature review with implications for referred cardiac pain. Br Dent J 2008;204:187–189.

80. Shih JJ, Devier D, Behr A. Late onset laryngeal and facial pain in previously asymptomatic vagus nerve stimulation patients. Neurology 2003;60:1214.

81. Carius A, Schulze-Bonhage A. Trigeminal pain under vagus nerve stimulation. Pain 2005;118:271–273.