Treatment of discolored vital teeth using peroxide bleaching agents have a high success rate [1] and can be performed following either at-home or in-office bleaching protocol [2]. Although the at-home bleaching treatment is the most popular one, many patients do not want to use a bleaching tray or do not want to wait several weeks to achieve the results [3,4] In this scenario, the in-office bleaching procedure is frequently request.

The in-office bleaching allows the control by the professional, avoids the exposition of soft tissues, reduces the risk material ingestion, reduces the incidence of gingival irritation and it has the best potential for immediate results [5,6]. However, some adverse effects have been widely reported in the literature, such as the sensitivity induced by in-office protocol [7-12]. In certain cases, the tooth sensitivity is so severe that some patients discontinue the treatment [13]. In attempt to explain this clinical situation, some current studies in molecular biology, have been carried out to elucidate this adverse event.

Sensitivity to the bleaching procedure seems to be the result from the facilitated passage of H2 O2 through enamel and dentin toward the pulp tissue [14] causing an inflammation process in this connective tissue [1]. Although the discomfort could be intense and responsible for the withdrawal of treatment in some cases, [15] this pain is usually mild and disappears within 48 hours after the bleaching treatment [10,15-17].A systematic review by Kielbassa et al., 2015 [18] about tooth sensitivity during and after vital tooth bleaching shows that tooth bleaching sensitivity continues to be an unsolved phenomenon that needs further follow-up with high quality studies. Despite this, some events that occur during and immediately after the procedure can clarify this side effect.

Free radicals, oxidation and sensitization of the dentin-pulp complex

H2 O2 is a free-radical derived from oxygen, thermally unstable, often found within the cells due intracellular reactions in some organelles, mainly mitochondria [19]. This chemical agent exhibit oxidative properties, [20-22] and in high concentrations have been used for treating discolored teeth [23].The main mechanisms responsible for the toxicity of peroxide compounds is associated with oxidative reactions and the consequent cellular damage caused by free-radicals [24]. Despite the well-known ability of free radicals to degrade the complex organic molecules that are responsible for tooth staining, [22] the exact mechanisms by which the teeth are whitened are not fully understood.

Besides, it has been reported that low molecular weight molecules of H2 O2 are capable of diffusing through the enamel and dentin and reach the pulp tissue [19]. Consequently, the H2 O2 and their degradation products can cause damage to pulp cells, especially in the odontoblast layer underlying the dentin [25]. According to Wataha et al., [26] the risk caused by dental materials on the dentin-pulp complex depends on the ability of the components to diffuse through enamel and dentin, reaching the dental pulp. Several studies have shown the diffusion process, [27,28] which is facilitated by their low molecular weight as well as its ability to denature tissue proteins [29]. Moreover, high concentrations of free-radicals in the bleaching gels increase the diffusion of H2 O2 through the enamel and dentin [24]

Ion channels and pulp sensitivity

Odontoblasts can act as sensory cells that modulate nociceptive transduction in dental pulpal nerve fibers. For instance, odontoblasts layer express mechanosensitive, [30] acidsensitive, [31] and thermosensitive transient receptor potential [32-34] ion channels. When opening of these cation-permeable ion channels cause a membrane potential producing inward currents. Odontoblasts also express voltage-gated Na+ channels [35]. However, the role of odontoblasts in dental sensitivity and the underlying cellular and molecular mechanisms for dental nociception initiation and transduction have not been fully established.

According to Markowitz et al., [15] dental sensitivity induced by bleaching gels can result from a direct activation of neuronal receptors by H2 O2 . The action potential transient receptor (TRPA1) could be the responsible for the pain induced by H2 O2 . Peroxides and other oxidizing agents can oxidize cysteine residues in TRPA1 ion channel, resulting on the receptor activation [36], and triggering pain. Besides, the intracellular reaction between peroxide and iron ions, producing oxygen radicals by the Fenton reaction, could also contribute to the activation of the cysteine residues into TRPA1 channel [37]. In fact, a long-term treatment with the tumor necrosis factor-alfa (TNF-α) used as an hypotonicity-inductor membrane stretch, resulted in upregulation of TRPA1 expression in human odontoblast-like cells, [38] indicating that this ion channel could be activated by a variety of inflammatory cytokines, making it a gatekeeper of inflammation [39].

Furthermore, it has been demonstrated that adenosine triphosphate (ATP) is released from the dental pulp upon external cold or mechanical dentin stimulation [40]. Moreover, odontoblasts may mediate nociceptive signaling via ATP release through the connexin [41,42] and pannexin channels [40,43]. ATP in turns can activate inotropic purinergic P2X3 receptors expressed in dental pulpal nerve fibers [44] and intercellular odontoblast neuron communication [45]. These findings support the importance of ATP signaling in mediating dentin hypersensitivity and dental pain [46]

Pulp swelling and necrosis

Pain is the result of activation of sensory structures called nociceptors [47,48]. Most of the nociceptors involved in the inflammatory pain process are polymodal (sensitive to different kind of stimuli) with a high excitability threshold. The ability to distinguish pain sensations resulting from pressure, heat or cold must involve decoding of noxious signals within the central nervous system [49].

It is believed that pain of dental pulp is a consequence of the inflammatory response [50,51] due to tissue damage [52]. Hence, vasodilation and increased vascular permeability occurs, resulting in edema formation and increased internal pressure. This stimulates nociceptors, which in turn triggers the pain [53]. It has been reported that the use of H2 O2 produce a transient inflammatory reaction in the pulp tissue14 and, as a consequence, the release of bradykinin [54] and substance P [55]. These two substances are known to be involved in pain and inflammation processes of dental pulp [55,56]. Moreover, some biological active mediators derived from the arachidonic acid could contribute to this process, since the cycloxygenase-2 (COX-2), an important enzyme in the inflammatory pathway, is up-regulated in inflamed tissues [57,58], and it has been shown to play important roles in human pulpal inflammation pathogenesis [59,60].

In fact, some studies have demonstrated that H2 O2 bleaching gel induces an inflammatory infiltrate and necrosis [61,62], and the number of bleaching sessions influences on the extent of damage in the pulp tissue directly [62].

Local control using topical agents

The dental sensitivity is the most common adverse reaction right after bleaching procedure, especially in anterior teeth [63], and it is mandatory to establish a protocol to prevent or treat the teeth sensitivity. The most successful approaches to reduce dental sensitivity after bleaching are achieved by topical application of a gel based on potassium nitrate and sodium fluoride [16,51], and by a product containing 2 – 8% glutaraldehyde and 25% - 50% 2-hydroxyethyl methacrylate (GLUMA) [10].The use of these local measures has been suggested as effective methods for controlling dental sensitivity after bleaching.

Systemic anti-inflammatory drugs

Preoperative and perioperative therapeutic schemes are currently proposed using systemic glucocorticoids [64] and nonsteroidal anti-inflammatory drugs (NSAIDs) [8,9,65] aiming to control the post procedure tooth sensitivity. Table 1 provides details regarding these studies. These therapeutic protocols have been justified by the inhibition of the pro-inflammatory mediators for long time, as central sensitization may not be prevented if the treatment is discontinued during the acute phase of inflammation [66].

Thus, drugs that prevent and treat the inflammatory process would be useful to control tooth sensitivity after bleaching process. However, dexamethasone, even at high daily doses, administered before and after of in-office tooth bleaching failed to prevent pain during and after bleaching. These findings suggest that production and release of inflammatory mediators could have a minor or no role at all in the development of tooth sensitivity induced by bleaching and, therefore, other mechanisms must be involved [64].

These outcomes are supported further by other studies where neither the 400mg ibuprofen8 nor 60mg etoricoxib9 administered in the perioperative managed to reduce sensitivity during and after tooth whitening, suggesting that prostaglandins blocking by the cyclooxygenase inhibition is not the main mechanism involved. However, the 600mg ibuprofen preoperative single dose was able to reduce sensitivity during but not after treatment [65]. This dose-depend response could be explained by the prostaglandins dependent analgesic effect of this agent, since ibuprofen can interact with sodium channels(Nav 1.7 and 1.8) reducing neuron hyperexcitability [67,68]; also inhibiting leukotrienes and other products from activated polymorph-nuclear leucocytes [69]; increasing the production of the endocannabinoid anandamide [70,71]; and affecting serotoninergic and noradrenergic pathways on the dorsal horn [72,73].

Although the mechanism of tooth sensitivity induced by bleaching is not well understood, the transient activation of some odontoblast and/or neuronal ion channels in the odontoblast layer by the H2 O2 could help to explain this phenomenon. Since local application of 5% potassium nitrate and 2% sodium fluoride gel [74] and GLUMA10 has been shown good clinical results with lower systemic risk, these effective methods should be appropriately used in order to reduce the risk of dental sensitivity after bleaching. Besides, this local application before dental bleaching did not affect the efficacy of H2 O2 bleaching agents [74].

There is a lack of clinical evidence to support the use of systemic anti-inflammatory drugs to control tooth sensitivity. In fact, the use of NSAIDs for reducing sensitivity after dental bleaching did not show any significant effect of preventive analgesia [75], maybe due to the lack of COX-2 expression on dental pulp after this procedure [9]. Furthermore, inflammatory mediators may not play an important role in the development of tooth sensitivity induced by H2 O2 . Nevertheless, since a preoperative single dose of 600mg ibuprofen was able to prevent the sensitivity during the in-office dental bleaching, it could be useful in special selected patients with a high sensibility risk predictor, as tooth sensitivity and surface loss [76]. Although ibuprofen is a nonprescription over-the-counter drug, it must be carefully indicated, especially in some medically compromised patients [73].

There is not enough clinical evidence to indicate systemic anti-inflammatory drugs to control tooth sensitivity after dental bleaching. Further studies are necessary to clarify the mechanism and systemic control of this tooth whitening side effect.

1. Giniger M, MacDonald J, Felix H. The clinical performance of professionally dispensed bleaching with added amorphous calcium phosphate. J Am Dent Assoc. 2005; 136: 383–392.

2. Bernardon JK, Sartori N, Ballarin A, Perdigão J, Lopes G, Baratieri LN. Clinical performance of vital bleaching techniques. Oper Dent. 2010; 35: 3–10.

3. Marson FC, Sensi LG, Vieira LC, Araújo E. Clinical evaluation of inoffice dental bleaching treatments with and without the use of lightactivation sources. Oper Dent. 2008; 33: 15-22.

4. Reis A, Kossatz S, Martins GC, Loguercio AD. Efficacy of and effect on tooth sensitivity of in-office bleaching gel concentrations: a randomized clinical trial. Oper Dent. 2013; 38: 386-393.

5. Gurgan S, Cakir FY, Yazici E. Different light-activated in-office bleaching systems: a clinical evaluation. Lasers Med Sci. 2010; 25: 817-822.

6. Tay LY, Kose C, Loguercio AD, Reis A. Assessing the effect of a desensitizing agent used before in office-tooth bleaching. J Am Dent Assoc. 2009; 140: 1245-1251.

7. LB HE, MY Shao, K Tan, Xu X, Li J-Y. The effects of light on bleaching and tooth sensitivity during in-office vital bleaching: a systematic review and metaanalysis. J Dent. 2012; 40: 644-653.

8. Paula E, Kossatz S, Fernandes D, Loguercio A, Reis A . The effect of perioperative Ibuprofen use on tooth sensitivity caused by in-office bleaching. Oper Dent. 2013; 38: 601-608.

9. de Paula EA, Loguercio AD, Fernandes D, Kossatz S, Reis A. Perioperative use of an antiinflammatory drug on tooth sensitivity caused by in-office bleaching: a randomized, triple-blind clinical trial. Clin Oral Investig. 2013; 17: 2091-2097.

10. Mehta D, Venkata S, Naganath M, LingaReddy U, Ishihata H, Finger WJ. Clinical trial of tooth desensitization prior to in-office bleaching. Eur J Oral Sci. 2013; 121: 477-481.

11. Bonafé E, Bacovis CL, Iensen S, Loguercio AD, Reis A, Kossatz S. Tooth sensitivity and efficacy of in-office bleaching in restored teeth. J Dent. 2013; 41: 363-369.

12. Al-Omiri MK, Al Nazeh AA, Kielbassa AM, Lynch E. Randomized controlled clinical trial on bleaching sensitivity and whitening efficacy of hydrogen peroxide versus combinations of hydrogen peroxide and ozone. Sci Rep. 2018; 8: 2407.

13. Chan W. Summary of: Side effects of external tooth bleaching: a multicentre practice-based prospective study. Br Dent J. 2013; 215: 466- 467.

14. Cooper JS, Bokmeyer TJ, Bowles WH. Penetration of the pulp chamber by carbamide peroxide bleaching agents J Endod. 1992; 18: 315-317.

15. Markowitz K. Pretty painful: why does tooth bleaching hurt? Med Hypotheses. 2010; 74: 835-840.

16. Reis A, Dalanhol AP, Cunha TS, Kossatz S, Loguercio A D. Assessment of tooth sensitivity using a desensitizer before light-activated bleaching. Oper Dent. 2011; 36: 12-17.

17. Bortolatto JF, Pretel H, Floros MC, Luizzi AAC, Dantas AAR, Fernandez E, et al. Low concentration H(2)O(2)/TiO_N in office bleaching: a randomized clinical trial. J Dent Res. 2014; 93(Suppl 7): 66-71.

18. Kielbassa AM, Maier M, Gieren AK, Eliav E. Tooth sensitivity during and after vital tooth bleaching: A systematic review on an unsolved problem. Quintessence Int. 2015; 46: 881-897.

19. Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Radic Biol Med. 2000; 28: 1387-1404.

20. Arwill T, Myrberg N, Soremark R. Penetration of radioactive isotopes through enamel and dentin. II. Transfer of 22Na in fresh and chemically treated dental tissues. Odontol Revy. 1969; 20: 47-54.

21. Hanks CT, Fat JC, Wataha JC, Corcoran JF. Cytotoxicity and dentin permeability of carbamide peroxide and hydrogen peroxide vital bleaching materials, in vitro. J Dent Res. 1993; 72: 931-938.

22. Tredwin CJ, Naik S, Lewis NJ, Scully C. Hydrogen peroxide toothwhitening (bleaching) products: review of adverse effects and safety issues. Br Dent J. 2006; 200: 371-376.

23. Zantner C, Beheim-Schwarzbach N, Neumann K, Kielbassa AM. Surface microhardness of enamel after different home bleaching procedures. Dent Mater. 2007; 23: 243-250.

24. Li Y. Biological properties of peroxide-containing tooth whiteners. Food Chem Toxicol. 1996; 34: 887-904.

25. Goldberg M, Smith AJ. Cells and extracellular matrices of dentin and pulp: a biological basis for repair and tissue engineering. Crit Rev Oral Biol Med. 2004; 15: 13-27.

26. Wataha JC, Hanks CT, Strawn SE, Fat JC. Cytotoxicity of components of resins and other dental restorative materials. J Oral Rehabil. 1994; 21: 453-462.

27. Benetti AR, Valera MC, Mancini MNG, Miranda CB, Balducci I. In vitro penetration of bleaching agents into the pulp chamber. Int Endontic J 2004; 37: 120-124. 

28. Gökay O, Müjdeci A, Algin E. In vitro peroxide penetration into pulp chamber from newer bleaching products. Int Endontic J. 2005; 38: 516-520.

29. Goldstein CE, Goldstein RE, Feinman RA, Garber DA. Bleaching vital teeth: state of the art. Quintessence Int. 1989; 20: 729-737.

30. Magloire H, Couble ML, Thivichon-Prince B, Maurin J-C, Bleicher F. Odontoblast: a mechanosensory cell. J Exp Zool Part B. 2009; 312B: 416–424.

31. Sole-Magdalena A, Revuelta EG, Menenez-Diaz I, Calavia MG, Cobo T, Garcia-Suarex O, et al. Human odontoblasts express transient receptor protein and acid-sensing ion channel mechanosensor proteins. Microsc Res Tech. 2011; 74: 457–463.

32. Son AR, Yang YM, Hong JH, Lee SI, Shibukawa Y, Shin DM. Odontoblast TRP channels and thermo/mechanical transmission. J Dent Res. 2009; 88: 1014–1019.

33. El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, et al. Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity. Pain. 2011; 152: 2211– 2223.

34. Tsumura M, Sobhan U, Muramatsu T, Sato M, Ichikawa H, Sahara Y, et al. TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium-calcium exchangers in rat odontoblasts. Cell Calcium. 2012; 52: 124–136.

35. Allard B, Magloire H, Couble ML, Maurin JC, Bleicher F. Voltage-gated sodium channels confer excitability to human odontoblasts: possible role in tooth pain transmission. J Biol Chem. 2006; 281: 29002–29010.

36. Andersson DA, Gentry C, Moss S, Bevan S. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008; 28: 2485-2494.

37. Sawada Y, Hosokawa H, Matsumura K, Kobayashi S. Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur J Neurosci. 2008; 27: 1131-1142.

38. El Karim I, McCrudden MT, Linden GJ, Abdullah H, Curtis TM, McGahon M, et al. TNF-α Induced p38MAPK Activation Regulates TRPA1 and TRPV4 Activity in Odontoblast-like Cells. Am J Pathol. 2015; 185: 2994-3002.

39. Bautista DM, Pellegrino M, Tsunozaki M. TRPA1: a gatekeeper for inflammation. Annu Rev Physiol. 2013; 75: 181-200.

40. Liu X, Wang C, Fujita T, Malmstrom HS, Nedergaard M, Ren YF, et al. External Dentin Stimulation Induces ATP Release in Human Teeth. J Dent Res. 2015; 94: 1259-1266.

41. Ikeda H, Suda H. Rapid penetration of lucifer yellow into vital teeth and dye coupling between odontoblasts and neighbouring pulp cells in the cat. Arch Oral Biol. 2006; 51: 123-128.

42. Liu X, Yu L, Wang Q, Pelletier J, Fausther M, Sevigny J, et al. Expression of ecto-ATPase NTPDase2 in human dental pulp. J Dent Res. 2012; 91: 261–267.

43. Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada y. Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol. 2011; 193: 1257-1274.

44. Alavi AM, Dubyak GR, Burnstock G. Immunohistochemical evidence for ATP receptors in human dental pulp. J Dent Res. 2001; 80: 476– 483.

45. Shibukawa Y, Sato M, Kimura M, Sobhan U, Shimada M, Nishiyama A, et al. Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction. Pflugers Arch. 2015; 467: 843–863.

46. Magloire H, Maurin JC, Couble ML, Shibukawa Y, Tsumura M, ThivichonPrince B, et al. Topical review. Dental pain and odontoblasts: Facts and hypotheses. J Orofac Pain. 2010; 24: 335-349.

47. Fried K, Sessle BJ, Devor M. The paradox of pain from tooth pulp: lowthreshold “algoneurons”? Pain. 2011; 152: 2685-2689.

48. Gibbs JL, Melnyk JL, Basbaum AI. Differential TRPV1 and TRPV2 channel expression in dental pulp. J Dent Res. 2011; 90: 765-770.

49. ulius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001; 413: 203-210.

50. Haywood VB. Treating sensitivity during tooth whitening. Compend Contin Educ Dent. 2005; 26(Suppl 3): 11-20.

51. Pashley DH, Tay FR, Haywood VB. Dentin hypersensitivity: Consensus based recommendations for the diagnosis and management of dentin hypersensitivity. Inside Dentistry. 2008; 1-35.

52. Bender IB. Pulpal pain diagnosis - a review. J Endod. 2000; 26: 175- 179.

53. Jara-Oseguera A, Nieto-Posadas A, Szallasi A, Islas LD, Rosenbaum T. Molecular mechanisms of TRPV1 channel activation. The Open Pain Journal. 2010; 3: 68-81.

54. Lepinski AM, Hargreaves KM, Goodis HE, Bowles WR. Bradykinin levels in dental pulp by microdialysis. J Endod. 2000; 26: 744-747.

55. Caviedes-Bucheli J, Ariza-Garcia G, Restrepo-Méndez S, Ríos-Osorio N, Lombana N, Muñoz HR. The effect of tooth bleaching on substance P expression in human dental pulp. J Endod. 2008; 34: 1462-1465.

56. Rodd HD, Boissonade FM. Substance P expression in human tooth pulp in relation to caries and pain experience. Eur J Oral Sci. 2000; 108: 467-474.

57. Tsai CH, Huang FM, Yang LC, Chou MY, Chang YC. Immunohistochemical localization of cyclooxygenase-2 in radicular cysts Int Endod J. 2002; 35: 854-858.

58. Tsai CH, Chou MY, Chang YC. The upregulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med. 2003; 32: 146-153.

59. Chang YC, Yang SF, Huang FM, Liu CM, Tai KW. Proinflammatory cytokines induce cyclooxygenase-2 mRNA and protein expression in human pulp cell cultures. J Endod. 2003; 29: 201-204.

60. Chang YC, Huang FM, Yang SF, Liu C-M, Lai C-C, Chan Y, et al. Induction of cyclooxygenase-2 mRNA and protein expression in human pulp cells stimulated with black-pigmented bacteroides. J Endod. 2003; 29: 240-243.

61. Roderjan DA, Stanislawczuk R, Hebling J, de Souza Costa CA, Reis A, Loguercio AD. Response of human pulps to different in-office bleaching techniques: preliminary findings. Braz Dent J. 2015; 26: 242-248.

62. Cintra LT, Benetti F, da Silva Facundo AC, Ferreira LL, Gomes- Filho JE, Ervolino E, et al. The number of bleaching sessions influences pulp tissue damage in rat teeth. J Endod. 2013; 39: 1576-1580.

63. Buchalla W, Attin T. External bleaching therapy with activation by heat, light or laser – a systematic review. Dent Mater. 2007; 23: 586- 596.

64. Rezende M, Bonafé E, Vochikovski L, Farago PV, Loguercio AD, Reis A, et al. Pre- and postoperative dexamethasone does not reduce bleaching-induced tooth sensitivity. A randomized, triple-masked clinical trial. J Am Dent Assoc. 2016; 147: 41-49.

65. Charakorn P, Cabanilla LL, Wagner WC, Foong WC, Shaheen J, Pregitzer R, et al . The effect of preoperative ibuprofen on tooth sensitivity caused by in-office bleaching. Oper Dent. 2009; 34: 131-135.

66. de Andrade ED. Prevenção e controle da dorIn: de Andrade ED (ed). Terapêutica Medicamentosa emOdontologia Editorial as Artes Médicas, São Paulo 2014: 43-53.

67. Gould HJ , England JD, Soignier RD, Nolan P, Minor LD, Liu ZP, et al. Ibuprofen blocks changes in Nav 1.7 and 1.8 sodium channels associated with complete Freund’s adjuvant-induced inflammation in rat. J Pain. 2004; 5: 270-280.

68. Huang ZJ, Hsu E, Li H-C, Rosner AL, Rupert RL, Song X-J. Topical application of compound Ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation. J Pain. 2011; 12: 141- 152.

69. Rainsford KD. Ibuprofen: from invention to an OTC therapeutic mainstay. Int J Clin Pract Suppl. 2013; 9-20.

70. Fowler CJ, Naidu PS, Lichtman A, Onnis V. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. Br J Pharmacol. 2009; 156: 412– 419.

71. Fowler CJ, Bj?rklund E, Lichtman AH, Naidu PS, Congiu C, Onnis V. Inhibitory properties of ibuprofen and its amide analogues towards the hydrolysis and cyclooxygenation of the endocannabinoid anandamide. J Enzyme Inhib Med Chem. 2013; 28: 172-182.

72. Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009; 17: 275–342.

73. Rainsford KD. Ibuprofen: Pharmacology, Therapeutics and Side Effects. Mechanisms of Inflammation and Sites of Action of NSAIDs In: KD Rainsford. London: Springer. 2012; 43-57.

74. do CarmoPúblio J, D’Arce MBF, Ambrosano GMB, Aguiar FHB, Lovadino JP, Paulillo LAMS, et al. Efficacy of tooth bleaching with the prior application of a desensitizing agent. J Investig Clin Dent. 2015; 6: 133-140.

75. Faria-E-Silva AL, Nahsan FP, Fernandes MT, Martins-Filho PRS. Effect of preventive use of nonsteroidal anti-inflammatory drugs on sensitivity after dental bleaching: a systematic review and metaanalysis. J Am Dent Assoc. 2015; 146: 87-93.

76. Bruzell EM, Pallesen U, Thoresen NR, Wallman C, Dahl JE. Side effects of external tooth bleaching: a multi-centre practice-based prospective study. Br Dent J. 2013; 215: E17

Dental sensitivity after in-office bleaching is the most common adverse effect produced by the hydrogen peroxide (H2O2) bleaching agents. Inflammatory processes induced by chemical mediators and direct activation of ion channels by H2O2 and oxidative products have been related to this side effect. However, current data suggest that production and release of inflammatory mediators may not play an important role in the development of tooth sensitivity induced by bleaching. Possible mechanisms of dental sensibility after in-office whitening are discussed in this literature review.

•    Anti-inflammatory
•    Hydrogen Peroxide
•    Tooth bleaching

Públio J, Burga-Sánchez J, Ferraz LN, Groppo FC, Aguiar FHB, et al. (2018) Preemptive and Preventive Systemic Anti-Inflammatory Drugs for Dental Sensitivity Control in-Office Bleaching. JSM Dent 6(3): 1112

TRPA1: The Action Potential Transient Receptor; TNF-Α: Tumor Necrosis Factor-Alfa; ATP: Adenosine Triphosphate; COX2: Cycloxygenase-2; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs