Korean J Pain.  2013 Oct;26(4):347-355. 10.3344/kjp.2013.26.4.347.

An Insight Into Neurophysiology of Pulpal Pain: Facts and Hypotheses

• Jain N
• Gupta A
• N M

• KMID: 2074042
• DOI: http://doi.org/10.3344/kjp.2013.26.4.347

Abstract

Pain and pain control are important to the dental profession because the general perception of the public is that dental treatment and pain go hand in hand. Successful dental treatment requires that the source of pain be detected. If the origin of pain is not found, inappropriate dental care and, ultimately, extraction may result. Pain experienced before, during, or after endodontic therapy is a serious concern to both patients and endodontists, and the variability of discomfort presents a challenge in terms of diagnostic methods, endodontic therapy, and endodontic knowledge. This review will help clinicians understand the basic neurophysiology of pulpal pain and other painful conditions of the dental pulp that are not well understood.

Keyword

inflammation; mediators; pulpal pain; pulpitis; sensory nerves

MeSH Terms

Dental Care
Dental Pulp
Hand
Humans
Inflammation
Neurophysiology
Pulpitis

Reference

1. Sessle BJ. Recent developments in pain research: central mechanisms of orofacial pain and its control. J Endod. 1986; 12:435–444. PMID: 3465847.

2. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc. 1993; 124:115–121. PMID: 8409001.

3. Estrela C, Guedes OA, Silva JA, Leles CR, Estrela CR, Pécora JD. Diagnostic and clinical factors associated with pulpal and periapical pain. Braz Dent J. 2011; 22:306–311. PMID: 21861030.

4. Byers MR. Dental sensory receptors. Int Rev Neurobiol. 1984; 25:39–94. PMID: 6206015.

5. Byers MR, Närhi MV. Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions. Crit Rev Oral Biol Med. 1999; 10:4–39. PMID: 10759425.

6. Bergenholtz G, Hørsted-Bindslev P, Reit C. Textbook of endodontology. 2nd ed. Oxford: Wiley-Blackwell Pub;2010. p. 33–35.

7. Ingle JI, Bakland LK, Baumgartner JC. Ingle's endodontics 6. Ontario: BC Decker;2008. p. 136–137.

8. Figdor D. Aspects of dentinal and pulpal pain. Pain of dentinal and pulpal origin--a review for the clinician. Ann R Australas Coll Dent Surg. 1994; 12:131–142. PMID: 7993042.

9. Närhi MV, Hirvonen TJ, Hakumäki MO. Responses of intradental nerve fibres to stimulation of dentine and pulp. Acta Physiol Scand. 1982; 115:173–178. PMID: 7136809.

10. Närhi M, Jyväsjärvi E, Virtanen A, Huopaniemi T, Ngassapa D, Hirvonen T. Role of intradental A- and C-type nerve fibres in dental pain mechanisms. Proc Finn Dent Soc. 1992; 88(Suppl 1):507–516. PMID: 1508908.

11. Matthews B, Vongsavan N. Interactions between neural and hydrodynamic mechanisms in dentine and pulp. Arch Oral Biol. 1994; 39(Suppl):87S–95S. PMID: 7702472.

12. Pashley DH. Mechanisms of dentin sensitivity. Dent Clin North Am. 1990; 34:449–473. PMID: 2197121.

13. Vongsavan N, Matthews B. The relationship between the discharge of intradental nerves and the rate of fluid flow through dentine in the cat. Arch Oral Biol. 2007; 52:640–647. PMID: 17303068.

14. Braennstroem M, Astroem A. A study on the mechanism of pain elicited from the dentin. J Dent Res. 1964; 43:619–625. PMID: 14183350.

15. Gomez N. Bibliographic update work: dental pulp sensory function. Pain. Electron J Endod Rosario. 2011; 10:540–552.

16. Närhi M, Yamamoto H, Ngassapa D. Function of intradental nociceptors in normal and inflamed teeth. In : Shimono M, Maeda T, Suda H, Takahashi K, editors. Dentin/pulp complex. Tokyo: Quintessence Pub. Co.;1996. p. 136–140.

17. Dong WK, Chudler EH, Martin RF. Physiological properties of intradental mechanoreceptors. Brain Res. 1985; 334:389–395. PMID: 3873270.

18. Jyväsjärvi E, Kniffki KD. Cold stimulation of teeth: a comparison between the responses of cat intradental A delta and C fibres and human sensation. J Physiol. 1987; 391:193–207. PMID: 3443945.

19. Trowbridge HO. Review of dental pain--histology and physiology. J Endod. 1986; 12:445–452. PMID: 3465848.

20. Hargreaves KM, Goodis HE, Seltzer S. Seltzer and Bender's dental pulp. Chicago (IL): Quintessence Pub. Co.;2002. p. 148–150.

21. Närhi MV. The characteristics of intradental sensory units and their responses to stimulation. J Dent Res. 1985; 64(Spec No):564–571. PMID: 3857258.

22. Bender IB. Pulpal pain diagnosis--a review. J Endod. 2000; 26:175–179. PMID: 11199715.

23. Närhi M, Virtanen A, Kuhta J, Huopaniemi T. Electrical stimulation of teeth with a pulp tester in the cat. Scand J Dent Res. 1979; 87:32–38. PMID: 284575.

24. Torebjörk HE, Hallin RG. Perceptual changes accompanying controlled preferential blocking of A and C fibre responses in intact human skin nerves. Exp Brain Res. 1973; 16:321–332. PMID: 4686614.

25. Närhi M, Yamamoto H, Ngassapa D, Hirvonen T. The neurophysiological basis and the role of inflammatory reactions in dentine hypersensitivity. Arch Oral Biol. 1994; 39(Suppl):23S–30S. PMID: 7702462.

26. Byers MR. Effects of inflammation on dental sensory nerves and vice versa. Proc Finn Dent Soc. 1992; 88(Suppl 1):499–506. PMID: 1508907.

27. Rutz JC, Hatton JF, Hildebolt C, Wells JE, Rowland KC. Localized increases in corticotropin-releasing factor receptors in pulp after dental injury. J Endod. 2007; 33:1319–1324. PMID: 17963955.

28. Jaber L, Swaim WD, Dionne RA. Immunohistochemical localization of mu-opioid receptors in human dental pulp. J Endod. 2003; 29:108–110. PMID: 12597708.

29. Dionne RA, Lepinski AM, Gordon SM, Jaber L, Brahim JS, Hargreaves KM. Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation. Clin Pharmacol Ther. 2001; 70:66–73. PMID: 11452246.

30. Chao D, Bazzy-Asaad A, Balboni G, Xia Y. delta-, but not mu-, opioid receptor stabilizes K(+) homeostasis by reducing Ca(2+) influx in the cortex during acute hypoxia. J Cell Physiol. 2007; 212:60–67. PMID: 17373650.

31. Fristad I, Bletsa A, Byers M. Inflammatory nerve responses in the dental pulp. Endod Topics. 2010; 17:12.

32. Kim S, Dörscher-Kim JE, Liu M. Microcirculation of the dental pulp and its autonomic control. Proc Finn Dent Soc. 1989; 85:279–287. PMID: 2635779.

33. Kim S, Dörscher-Kim JE, Lipowsky HH. Quantitative assessment of microcirculation in the rat dental pulp in response to alpha- and beta-adrenergic agonists. Arch Oral Biol. 1989; 34:707–712. PMID: 2624562.

34. Wakisaka S, Ichikawa H, Akai M. Distribution and origins of peptide- and catecholamine-containing nerve fibres in the feline dental pulp and effects of cavity preparation on these nerve fibres. J Osaka Univ Dent Sch. 1986; 26:17–28. PMID: 2435878.

35. Nup C, Rosenberg P, Linke H, Tordik P. Quantitation of catecholamines in inflamed human dental pulp by high-performance liquid chromatography. J Endod. 2001; 27:73–75. PMID: 11491641.

36. Hargreaves KM, Swift JQ, Roszkowski MT, Bowles W, Garry MG, Jackson DL. Pharmacology of peripheral neuropeptide and inflammatory mediator release. Oral Surg Oral Med Oral Pathol. 1994; 78:503–510. PMID: 7528373.

37. Sacerdote P, Levrini L. Peripheral mechanisms of dental pain: the role of substance P. Mediators Inflamm. 2012; 2012:951920. PMID: 22474402.

38. Kido MA, Ibuki T, Danjo A, Kondo T, Zhang JQ, Yamaza T, et al. Immunocytochemical localization of the neurokinin 1 receptor in rat dental pulp. Arch Histol Cytol. 2005; 68:259–265. PMID: 16477146.

39. Caviedes-Bucheli J, Gutierrez-Guerra JE, Salazar F, Pichardo D, Moreno GC, Munoz HR. Substance P receptor expression in healthy and inflamed human pulp tissue. Int Endod J. 2007; 40:106–111. PMID: 17229115.

40. Bowles WR, Withrow JC, Lepinski AM, Hargreaves KM. Tissue levels of immunoreactive substance P are increased in patients with irreversible pulpitis. J Endod. 2003; 29:265–267. PMID: 12701777.

41. Caviedes-Bucheli J, Azuero-Holguin MM, Gutierrez-Sanchez L, Higuerey-Bermudez F, Pereira-Nava V, Lombana N, et al. The effect of three different rotary instrumentation systems on substance P and calcitonin gene-related peptide expression in human periodontal ligament. J Endod. 2010; 36:1938–1942. PMID: 21092809.

42. Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations. Pharmacol Rev. 1986; 38:179–226. PMID: 3534898.

43. Ichikawa H, Sugimoto T. Vanilloid receptor 1-like receptor-immunoreactive primary sensory neurons in the rat trigeminal nervous system. Neuroscience. 2000; 101:719–725. PMID: 11113320.

44. Caviedes-Bucheli J, Azuero-Holguin MM, Munoz HR. The effect of capsaicin on substance P expression in pulp tissue inflammation. Int Endod J. 2005; 38:30–33. PMID: 15606820.

45. Lin SK, Kuo MY, Wang JS, Lee JJ, Wang CC, Huang S, et al. Differential regulation of interleukin-6 and inducible cyclooxygenase gene expression by cytokines through prostaglandin-dependent and -independent mechanisms in human dental pulp fibroblasts. J Endod. 2002; 28:197–201. PMID: 12017180.

46. Sundqvist G, Rosenquist JB, Lerner UH. Effects of bradykinin and thrombin on prostaglandin formation, cell proliferation and collagen biosynthesis in human dental-pulp fibroblasts. Arch Oral Biol. 1995; 40:247–256. PMID: 7605251.

47. Coon D, Gulati A, Cowan C, He J. The role of cyclooxygenase-2 (COX-2) in inflammatory bone resorption. J Endod. 2007; 33:432–436. PMID: 17368333.

48. Tani-Ishii N, Wang CY, Stashenko P. Immunolocalization of bone-resorptive cytokines in rat pulp and periapical lesions following surgical pulp exposure. Oral Microbiol Immunol. 1995; 10:213–219. PMID: 8602333.

49. Wisithphrom K, Murray PE, Windsor LJ. Interleukin-1 alpha alters the expression of matrix metalloproteinases and collagen degradation by pulp fibroblasts. J Endod. 2006; 32:186–192. PMID: 16500223.

50. Ueda L, Matsushima K. Stimulation of plasminogen activator activity and matrix metalloproteinases of human dental pulp-derived cells by tumor necrosis factor-alpha. J Endod. 2001; 27:175–179. PMID: 11487146.

51. D'Souza R, Brown LR, Newland JR, Levy BM, Lachman LB. Detection and characterization of interleukin-1 in human dental pulps. Arch Oral Biol. 1989; 34:307–313. PMID: 2688611.

52. Hosoya S, Ohbayashi E, Matsushima K, Takeuchi H, Yamazaki M, Shibata Y, et al. Stimulatory effect of interleukin-6 on plasminogen activator activity from human dental pulp cells. J Endod. 1998; 24:331–334. PMID: 9641108.

53. Barkhordar RA, Hayashi C, Hussain MZ. Detection of interleukin-6 in human dental pulp and periapical lesions. Endod Dent Traumatol. 1999; 15:26–27. PMID: 10219150.

54. Proctor ME, Turner DW, Kaminski EJ, Osetek EM, Heuer MA. Determination and relationship of C-reactive protein in human dental pulps and in serum. J Endod. 1991; 17:265–270. PMID: 1940751.

55. Güven G, Altun C, Günhan O, Gurbuz T, Basak F, Akbulut E, et al. Co-expression of cyclooxygenase-2 and vascular endothelial growth factor in inflamed human pulp: an immunohistochemical study. J Endod. 2007; 33:18–20. PMID: 17185121.

56. Holt CI, Hutchins MO, Pileggi R. A real time quantitative PCR analysis and correlation of COX-1 and COX-2 enzymes in inflamed dental pulps following administration of three different NSAIDs. J Endod. 2005; 31:799–804. PMID: 16249722.

57. Spoto G, Fioroni M, Rubini C, Tripodi D, Perinetti G, Piattelli A. Aspartate aminotransferase activity in human healthy and inflamed dental pulps. J Endod. 2001; 27:394–395. PMID: 11487132.

58. Spoto G, Fioroni M, Rubini C, Tripodi D, Di Stilio M, Piattelli A. Alkaline phosphatase activity in normal and inflamed dental pulps. J Endod. 2001; 27:180–182. PMID: 11487147.

59. Warren CA, Mok L, Gordon S, Fouad AF, Gold MS. Quantification of neural protein in extirpated tooth pulp. J Endod. 2008; 34:7–10. PMID: 18155483.

60. Wells JE, Rose ET, Rowland KC, Hatton JF. Kv1.4 subunit expression is decreased in neurons of painful human pulp. J Endod. 2007; 33:827–829. PMID: 17804321.