Innovations for combating Dentin Hypersensitivity: Current State of the Art

Yiming Li, DDS, MSD, PhD

Keywords: dentin hypersensitivity, exposed dentin, desensitizing toothpaste, tooth sensitivity

Dentin hypersensitivity commonly known as tooth sensitivity, is among the complaints most often cited by patients seeking dental treatment.¹ Strassler and coworkers² called tooth sensitivity the common cold of dentistry.” Studies have reported that dentin hypersensitivity affects up to 57% of dental patients of varying lifestyles and cultures, and it appears to peak between 20 to 40 years of age.^1,3-9

As recently discussed by Ajcharanukul et al,¹⁰ dentin hypersensitivity is a short, sharp pain arising from exposed dentin in response to stimuli—which are typically thermal, evaporative, tactile, osmotic, or chemical—and it cannot be ascribed to any other form of dental defect or pathology. The di comfort or pain of dentin hypersensitivity can be unpleasant and bothersome. However, in severe cases, it may have a significant negative impact on an individual’s daily life, as it may cause difficulties in eating and drinking, especially items with hot and cold temperatures; under certain circumstances, it may even interfere with speaking. Yet, the sensation of dentin hypersensitivity is highly subjective, and its occurrence and severity can be episodic. Consequently, a patient experiencing tooth sensitivity may not be able to pinpoint the causative tooth or teeth. Current methods for detection and diagnosis of dentin hypersensitivity essentially rely on delivering a tactile or air-blast stimulus to the suspected tooth, and the judgment is made on the basis of the patient’s description of the consequential sensation.^11-13

Due to its high prevalence in the general population and its impact on patients, dentin hypersensitivity has become a major research focus in dentistry. Significant progress has been made in understanding the problem and devising treatment regimens for combating dentin hypersensitivity. Recently introduced novel technology using 8% arginine and calcium carbonate in oral hygiene formulations to treat and control dentin hypersensitivity has attracted significant attention, because numerous clinical studies have demonstrated not only the product’s effectiveness, but also its ability to provide instant relief. This paper provides an overview of the etiology of dentin hypersensitivity, the discovery and development of measures for combating the problem, and the available data on clinical efficacy of products based on 8% arginine and calcium carbonate.

Etiology of Dentin Hypersensitivity

Significant efforts have been made to understand the etiology and mechanisms involved in the development of dentin hypersensitivity. Among the factors identified as being associated with dentin hypersensitivity are: gingival recession; periodontal disease; deep tooth cracks; and loss of enamel, cementum, and dentin due to mechanical abrasion, chemical erosion, and tooth fracture.^3,14

A common key characteristic of the etiologic factors for dentin hypersensitivity is exposed dentin, which allows the stimuli to affect the dentin tubular fluid and consequently activate the pulpal nerves for the perception of pain by the patient. The hydrodynamic theory was first proposed by Kramer¹⁵ in 1955 and later confirmed and developed by Brännström,¹⁶ whose in vivo studies correlated tooth sensitivity associated with applied pressure, air blasts, and chemical stimuli to in vitro measurements of dentin fluid shifts in response to these stimuli. Results of further research suggest that the pain sensation is caused by the activation of mechanoreceptors in intratubular nerves or in the superficial pulp due to changes of the flow and/or volume of fluid within dentinal tubules.^14,17 Reports in which 60% to 98% of patients experience dentin hypersensitivity following periodontal treatment have provided supportive evidence for this theory, as such procedures often result in dentin exposure.^3,14,18

Tooth bleaching using peroxide-based materials is also known to cause tooth sensitivity.^19-21 In most cases, the sensation is mild to moderate, and it is usually transient, dissipating spontaneously without specific treatment. The tooth sensitivity observed in tooth bleaching may or may not be associated with exposed dentin.

Measures to combat Dentin Hypersensitivity

A variety of chemicals, products, and measures have been used by professionals in the office or by patients at home to combat dentin hypersensitivity. In general, there are two approaches or mechanisms designed to reduce or eliminate dentin hypersensitivity: 1) depolarizing excited nerves in dentin tubules and pulp to disrupt neural response to pain stimuli; and 2) eliminating or minimizing the flow of dentin tubular fluid by sealing the exposed dentin, which is based on the hydrodynamic theory.

Application of potassium salts—most commonly potassium nitrate—is the primary means used to depolarize the excited nerve.^22,23 Potassium nitrate diffuses through the exposed dentin tubules to the pulp, where it exerts its calming effect on the nerve by affecting the transmission of nerve impulses. This effect was shown by Markowitz and coworkers,²⁴ whose study used cats as the animal model. In their study, the nerve activities of cat teeth were reduced by potassium, but not sodium salts. More recently, Ajcharanukul et al¹⁰ reported on the efficacy of potassium on dentin hypersensitivity in the first study using human premolars scheduled for extraction. Dentin of the buccal cusp tip was exposed, etched with acid, and covered with saline. Then, 3.7% potassium chloride was applied to the surface under 150-Hg hydrostatic pressure for 4 minutes, which presumably provides more potassium ions to dentin and pulp than brushing teeth with toothpaste with 5% potassium nitrate for 1 minute. The results of Ajcharanukul et al¹⁰ appear to support the findings reported in an early study by Hodosh²⁵ in which the best desensitizing effect of a topically applied potassium nitrate solution was achieved using a concentration of 15% or higher. These findings may help explain that, while toothpastes with 2% potassium salts as active ingredients have generally been recognized for their efficacy in reducing dentin hypersensitivity, clinical data indicate that their effect is gradual, requiring twice daily brushing for a period of 2 weeks or longer to provide significant relief from dentin hypersensitivity. Despite the availability of clinical efficacy data, there have been questions and debates on the desensitizing efficacy of potassium-based toothpastes. Specifically, a Cochrane systemic review and meta-analysis of a subset of six randomized, controlled clinical studies led its authors to conclude that the clinical efficacy in reducing dentin hypersensitivity of potassium-containing toothpastes is equivocal.²³

For the approach of occluding open dentin tubules, various agents, materials, and measures have been used, including strontium compounds, fluoride, casein phosphopeptide (CPP), potassium oxalate, resin sealers, and lasers.^14,26-30 So far, there has been little research on using lasers for reducing dentin hypersensitivity; the use of resin sealers and potassium oxalate is limited to certain patients for practical reasons; and the evidence supporting the use of fluoride in toothpaste as a desensitizing agent for dentin hypersensitivity has been minimal. However, both strontium compounds and CPP have been incorporated into oral hygiene products with the objective of reducing dentin hypersensitivity.

CPP is a casein derivative and is capable of stabilizing calcium phosphate—which is usually insoluble—in a state-forming CPP-amorphous calcium phosphate (ACP) complex.^31,32 MI Paste™ Plus (GC America Inc., www.gcamerica com) is a product containing CPP-ACP; it is designed to promote remineralization through the deposition of fluoride-containing calcium-phosphate precipitates, which has been suggested for reducing the risks of dental caries and dentin hypersensitivity. However, so far, the results published in the literature are inconsistent.^27,30,32-34 A 2008 systematic review of the literature²⁹ concluded that “there is insufficient clinical trial evidence (in quantity, quality or both) to make a r commendation regarding the long-term effectiveness of casein derivatives,
specifically CPP-ACP, in preventing caries in vivo and in treating dentin hypersensitivity or dry mouth.” The authors questioned the potential possibility of interactions between fluoride and ACP that may precipitate out as calcium fluoride, rendering both inorganic components ineffective. They also expressed their concerns about the 900 ppm fluoride in the product and, therefore, r commended against its use for children younger than 6 years of age.

Among the variety of agents and materials used historically to occlude dentin tubules, strontium compounds are among the first being used in toothpaste for teeth with dentin hypersensitivity. Approximately 50 years ago—prior to the widespread adoption of potassium as a desensitizer—strontium chloride was incorporated into toothpaste because it was believed to treat tooth sensitivity by occluding dentin tubules. Recently, strontium acetate has been used in desensitizing toothpastes because of its compatibility with fluoride.³⁵ However, data on their clinical efficacy for the relief of dentin hypersensitivity are inconsistent and equivocal, at best.^36-38 A recent literature review identified a range of clinical studies on the effects of strontium-based toothpastes on dentin hypersensitivity when used during routine brushing for periods of 4 to 12 weeks; however, the review determined that many of the double-blind, controlled studies showed no significant benefit for 10% strontium chloride or 8% strontium acetate toothpastes compared to regular fluoride toothpaste. For this reason, the author concluded that: 1) the evidence for the efficacy of strontium-based toothpaste in reducing dentin hypersensitivity during long-term use is, at best, equivocal; and 2) there is no evidence to suggest that strontium-based toothpaste can provide immediate relief of sensitivity when directly applied to sensitive teeth.³⁸

Consequently, in addition to the use of potassium salts in toothpaste for nerve depolarization to disrupt neural response to pain stimuli, efforts have been made to develop formulations that are capable of occluding the open dentin tubules to minimize or eliminate the flow of dentin fluids. More recently, a novel technology using 8% arginine—an amino acid found naturally in saliva—and calcium carbonate has been introduced to control dentin hypersensitivity.^38,39 The arginine in saliva is incapable of quickly plugging and sealing open dentin tubules and thereby providing immediate reduction of dentin hypersensitivity; however, research using advanced science and technology has succeeded in achieving such an efficacy by utilizing this mechanism of arginine and calcium carbonate in dental prophylactic paste and toothpaste. An arginine-based desensitizing prophylaxis paste, originally called ProClude^® Desensitizing Prophylaxis Paste and marketed by Ortek Therapeutics, Inc. (www.ortekinc com), demonstrated its clinical effectiveness in providing instant sensitivity relief when it was applied to sensitive teeth following scaling and root planing; furthermore, this sensitivity relief lasted for at least 28 days after a single application.^38,40 The mechanism of action of this new technology—now marketed under the name Colgate^® Sensitive Pro-Relief™ Desensitizing Paste (Colgate Professional, www.colgateprofessional com)—has been investigated using atomic force microscopy, confocal laser scanning microscopy, electron spectroscopy, and high-resolution scanning electron microscopy; the results show that the formed sealing plugs are composed of arginine, calcium, phosphate, and carbonate.^41,42 Furthermore, hydraulic conductance studies have shown that the strength of these dentin plugs is adequate to withstand normal pulpal pressures and acid challenge, effectively reducing the dentin fluid flow^40,41 and, consequently, the sensation of tooth sensitivity.^38,39,43,44

Clinical Efficacy and Safety of Dental Prophylaxis Paste Containing 8% Arginine and Calcium Carbonate

Colgate Sensitive Pro-Relief desensitizing prophylaxis paste is the first dental product that uses 8% arginine and calcium carbonate as active ingredients. Dental prophylaxis is a routine and effective procedure for reducing risks associated with dental plaque and calculus; it also removes tooth surface stains. The use of a prophylaxis paste enhances the cleaning efficacy and polishes the cleaned tooth surfaces. However, the process of scaling and polishing can increase the risk of dentin hypersensitivity, especially in those with exposed dentin. The unpleasant sensation of dentin hypersensitivity after dental prophylaxis can temporarily interfere with normal oral hygiene practice and even eating and drinking; thus, an individual may be discouraged from maintaining a regular dental prophylaxis schedule. Consequently, a prophylaxis paste that also provides effective desensitizing efficacy to reduce post-procedure dentin hypersensitivity is highly desirable.⁴³

Two studies in the literature have reported on the clinical efficacy of Pro-Relief desensitizing prophylaxis paste.^45,46 Hamlin’s group⁴⁵ conducted a double-blind clinical investigation to compare the clinical efficacy of Colgate Sensitive Pro-Relief desensitizing prophylaxis paste in reducing dentin hypersensitivity to that of a control paste (Nupro^® pumice-based prophylaxis paste, DENTSPLY, www.dentsply com) in 45 adults. Yeaple tactile and Schiff cold air-blast methods were used to determine dentin hypersensitivity. The assigned paste was applied immediately before the professional dental prophylaxis procedure. After the completion of dental cleaning, dentin hypersensitivity was again evaluated following the same methods. The investigators detected a significant reduction in dentin hypersensitivity in subjects who received Colgate Sensitive Pro-Relief desensitizing prophylaxis paste immediately after the completion of the prophylaxis (P < 0.05); the improvement compared to the baseline tactile and air-blast hypersensitivity scores were 132.1% and 48.6%, respectively. The average tactile scores before (16.52) and after (20.1) prophylaxis for control subjects were not statistically significant, although their air-blast score exhibited a statistical improvement (13.9%); that improvement, however, was much smaller than that achieved by the Colgate Sensitive Pro-Relief prophylaxis paste. When the two groups were compared, Colgate Sensitive Pro-Relief desensitizing prophylaxis paste was significantly more effective than the control prophylaxis paste for reducing dentin hypersensitivity, as evidenced by additional improvements of 110% and 41.9% in tactile and air-blast hypersensitivity scores, respectively.

Schiff and coworkers⁴⁶ reported their findings from a double-blind study of 68 adults that examined the clinical efficacy and safety of the same two dental prophylaxis pastes using a complementary study design and procedures similar to those in the above-described study by Hamlin et al.⁴⁵ The key differences in study design were that the assigned paste was applied immediately after the oral prophylaxis, and there were additional evaluations of tactile and air-blast dentin hypersensitivity to those measured immediately after a single application of either Colgate Sensitive Pro-Relief desensitizing prophylaxis paste or Nupro pumice prophylaxis paste at 4 and 12 weeks. The data collected immediately after the application of the assigned prophylaxis paste are consistent with and confirmatory of the findings reported by Hamlin et al.⁴⁵ Colgate Sensitive Pro-Relief prophylaxis paste maintained its efficacy of reduced dentin hypersensitivity achieved immediately after the application (156.2% and 44.1% for tactile and air-blast hypersensitivity scores, respectively) for 4 weeks (173.0% and 45.9% for tactile and air-blast hypersensitivity scores, respectively), while the improvement of the control paste at the post-application (43.1% and 15.1% for tactile and air-blast hypersensitivity scores, respectively) had largely dissipated at 4 weeks (8.3% and 8.9% for tactile and air-blast hypersensitivity scores, respectively). The 12-week mean tactile and air-blast hypersensitivity scores were statistically comparable to those at the post-scaling baseline for both pastes.

Both studies^45,46 found no abnormalities of oral tissues or any other clinical adverse effects of the Colgate Sensitive Pro-Relief desensitizing prophylaxis paste or Nupro pumice prophylaxis paste. In addition, in vitro studies reported no evidence of negative effect by Colgate Sensitive Pro-Relief desensitizing prophylaxis paste on the surface roughness of a resin composite, porcelain, amalgam, gold alloy, and human enamel,⁴⁷ as well as on shear bond strength of composites to human enamel.⁴⁸

The author of the present article also led a double-blind study (unpublished data) that evaluated the clinical efficacy of Colgate Sensitive Pro-Relief desensitizing prophylaxis paste as compared to MI Paste Plus and Nupro-M paste on dentin hypersensitivity reduction immediately after application and over 4 weeks following a single treatment in 120 adults. Subjects received a scaling procedure and then a single application of the assigned paste. Dentin hypersensitivity was examined using the Yeaple tactile and Schiff air-blast methods prior to the scaling (baseline), immediately after the treatment, and after 4 weeks. All three groups showed a significant reduction in the tactile and air-blast dentin hypersensitivity immediately and after 4 weeks following the single application (P < 0.05). The subjects of the Pro-Relief group exhibited a significant improvement in mean tactile and air-blast dentin hypersensitivity scores as compared to both the other pastes (P < 0.05). Many subjects who expressed their pleasant surprise at the instant effectiveness in relieving tooth sensitivity and who inquired about the name of the paste used on them were found after the completion of the study to be in the group that received Colgate Sensitive Pro-Relief desensitizing prophylaxis paste. A comprehensive examination of oral soft and hard tissues detected no evidence of any abnormalities or adverse changes of the tissues throughout the 4-week study period. In addition, when questioned, none of the subjects reported any experience of adverse effects—related or unrelated to the study products—at any of the clinical visits. The overall results are consistent with and supportive of those reported by Hamlin et al⁴⁵ and Schiff et al.⁴⁶

Clinical Efficacy and Safety of Toothpaste Containing 8% Arginine and Calcium Carbonate

To date, nine clinical studies have been reported on a toothpaste containing 8% arginine as the active ingredient with calcium carbonate and 1450 ppm fluoride as sodium monofluorophosphate (MFP) for controlling dentin hypersensitivity. These studies involved populations in Canada,^49,50 China,^51,52 Italy,^53,54 and United States^55-57; all found significant efficacy of this arginine/calcium carbonate toothpaste in reducing dentin hypersensitivity.

Three similar studies in Canada (120 subjects),⁴⁹ China (122 subjects),⁵² and United States (125 subjects)⁵⁶ also reported significant reductions in dentin hypersensitivity immediately after a single topical application of the arginine/calcium carbonate toothpaste, as well as after 3 days of twice daily toothbrushing—as compared to regular fluoride toothpaste as a negative control. Ayad’s⁴⁹ and Nathoo’s studies⁵⁶ showed that toothpaste containing 8% arginine and 1450 ppm fluoride as MFP in a calcium carbonate base provided significant relief of dentin hypersensitivity immediately following a single direct application to sensitive teeth when compared to a potassium-based desensitizing toothpaste; the potassium-based desensitizing toothpaste, in contrast, did not provide significant instant relief. Another clinical study of 84 subjects, which was conducted by Schiff’s team,⁵⁵ compared the efficacy of the toothpaste containing arginine and calcium carbonate in providing instant relief of dentin hypersensitivity when delivered as a single direct topical application using a cotton swab applicator versus using a fingertip. The study also evaluated the effect on dentin hypersensitivity of this toothpaste after 7 days of twice daily brushing at home. The data showed that, immediately after direct topical application of the arginine/calcium carbonate toothpaste using either the fingertip or swab, test teeth exhibited statistically significant improvements (P < 0.05) from baseline in tactile hypersensitivity scores (191.7% and 182.1%, respectively) and air-blast hypersensitivity scores (58.1% and 56.3%, respectively). After the 7-day daily toothbrushing, the improvements remained significant (P < 0.05) in both the tactile (191.7% and 190.5%, respectively) and air-blast scores (57.4% and 58.2%, respectively) for either group. The improvements in dentin hypersensitivity reduction were not statistically significant immediately after the topical application and after 7 days of twice daily brushing with the toothpaste.

Four double-blind, randomized clinical studies^50,51,53,54 compared the efficacy of the toothpaste containing 8% arginine and 1450 ppm fluoride as MFP in a calcium carbonate base to a potassium-based desensitizing toothpaste in reducing dentin hypersensitivity after 2, 4, and 8 weeks of twice daily toothbrushing at home. The data demonstrated that the arginine/calcium carbonate toothpaste was effective in controlling dentin hypersensitivity at all three study time points and provided superior relief of dentin hypersensitivity compared to the potassium-based desensitizing toothpaste control. The results were consistent and mutually confirmatory among the four studies.

An 8-week longitudinal clinical study of 77 subjects compared an 8% strontium acetate-based dentifrice to the 8% arginine/calcium carbonate dentifrice in their efficacy in reducing dentin hypersensitivity.⁵⁷ Subjects brushed their teeth with the assigned toothpaste twice daily, and their tooth sensitivity was determined using the same Schiff air-blast and Yeaple probe methods on weeks 2, 4, and 8. The results showed that both toothpastes were effective in reducing dentin hypersensitivity; the effect was comparable for the two toothpastes for any of the time points and measures, except for the tactile sensitivity at week 8, for which the strontium acetate-based toothpaste showed a statistically higher improvement (P = 0.0391) compared to the arginine/calcium carbonate toothpaste. However, it appears that the overall effects observed in Hughes’s study⁵⁷ are lower than those previously reported for the 8% arginine/calcium carbonate toothpaste.^50,52,55,56

All the above nine clinical studies^49-57 found no abnormalities of oral tissues or any other clinical adverse effects associated with the use of toothpaste containing 8% arginine and 1450 ppm fluoride as MFP in a calcium carbonate base. A recent clinical study found no negative effect of twice daily use of toothpaste containing 8% arginine and 1450 ppm fluoride as MFP in a calcium carbonate base on supragingival calculus formation and gingivitis.⁵⁸

Summary and Conclusions

The unpleasant nature of dentin hypersensitivity and its high prevalence in the general population have attracted great research interest and have led to the promotion of significant advancements in developing innovative measures for its effective and safe control. One such recent advance was the introduction of a novel toothpaste and a dental prophylaxis paste using 8% arginine and calcium carbonate as the active ingredients. The review of the research available in the literature demonstrates that both the arginine/calcium carbonate dental prophylaxis paste and toothpaste are highly effective in reducing dentin hypersensitivity. A unique and unprecedented strength of the arginine/calcium carbonate formulations is their ability to provide instant relief of dentin hypersensitivity. The data from these studies—which were generated by multiple investigators using various study populations in different countries—are highly consistent and mutually confirmatory and supportive.

Disclosure

Preparation of this article was supported by portions of research grants from Colgate-Palmolive company.

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About the Author

Yiming Li, DDS, MSD, PhD
Professor and Director, Center for Dental Research
Loma Linda University School of Dentistry
Loma Linda, California