Comparison of efficacy of three commercially available dentifrices on dentinal hypersensitivity: a randomized clinical trial
This article is corrected by:
- Errata: Errata Volume 58, Issue 2, 272, Article first published online: 28 May 2013
[Correction added on 16 October 2012, after first online publication: Author list and affiliations have been corrected.]
Dr AR Pradeep
Professor and Head
Department of Periodontics
Government Dental College and Research Institute
Background: Dentinal hypersensitivity has been defined as a short, sharp pain arising from exposed dentine as a result of various stimuli such as heat, cold, chemical, or osmotic, that cannot be ascribed to any other pathology. This study was conducted to assess the efficacy of three commercially available toothpastes in the reduction of dentinal hypersensitivity.
Methods: A total of 149 subjects (72 males and 77 females; aged 20 to 60 years) were entered into the study and randomly divided into four groups: Group 1 – toothpaste containing 5% potassium nitrate; Group 2 – toothpaste containing 5% calcium sodium phosphosilicate with fused silica; Group 3 – toothpaste containing 3.85% amine fluoride; and Group 4 – a placebo toothpaste. After sensitivity scores for controlled air stimulus and cold water at baseline were recorded, subjects were given toothpastes and sensitivity scores were measured again at 2 weeks and 6 weeks.
Results: All groups showed a reduction in sensitivity scores at 2 weeks and 6 weeks. The calcium sodium phosphosilicate group was found to be significantly better compared to the other groups at the end of 6 weeks.
Conclusions: The calcium sodium phosphosilicate group showed a better reduction in the symptoms of dentinal hypersensitivity.
Abbreviations and acronyms:
analysis of variance
Dentinal hypersensitivity (DH) has been defined as a short, sharp pain arising from exposed dentine as a result of various stimuli such as heat, cold, chemical, or osmotic, that cannot be ascribed to any other pathology.1 The incidence of DH may affect patients of any age and reportedly peaks during the third and fourth decades of life.2 The condition may affect any tooth, but it most often affects canines and premolars.3 There is a wide variation in the literature regarding the distribution patterns of affected teeth.4 DH can manifest if dentine is exposed by loss of enamel (due to abrasion, erosion or attrition), keeping the tubules open on the dentine surface. The constant action of acids or loss of structure such as cementum denudes the root surface, which is prone to removal by brushing or periodontal treatment,5 or more commonly, by the association of two or more of these factors.6 It may also be caused by gingival recession which physiologically occurs with ageing or pathologically due to chronic periodontal disease or the patient’s deleterious habits.7
Braennstroem and Astroem in 1964 proposed the ‘hydrodynamic theory’ which is widely accepted as the explanation of the pain caused by DH.8 According to this theory, the opening of dentinal tubules due to loss of enamel and cementum in the cervical areas may stimulate the pulp nerves due to the movement of dentinal fluid inside the tubules. This may result in the sensation of pain. Also, bacteria and their elements may diffuse from the oral cavity to the pulp through the open dentinal tubules, resulting in localized inflammatory response.9 Histologically, under transmission electron microscope, a sensitive tooth shows two times larger tubules and an increased number per area compared to a normal tooth without DH.10 Although macroscopically the dentine of a hypersensitive tooth does not differ from that of a normal tooth, the symptoms suggest minor inflammation of pulp.11
Currently, two major approaches are commonly employed in the treatment and prevention of DH: occlusion of tubules and nerve activity blockage. In the tubular occlusion approach, the tooth is treated with an agent that occludes the dentinal tubules, thus resulting in stoppage of pulpal fluid flow, leading to reduction in DH.12,13 Treatment strategies such as lasers, dentine sealers and periodontal soft tissue grafting work on the same principle. In the blockage of nerve activity, potassium ions cause a depolarization of the cellular membrane of the nerve terminal by concentrating on dentinal tubules and thus giving rise to a refractory period with decreased sensitivity.14
Desensitizing agents have been classified according to various criteria such as their reversible or irreversible characteristics, their mode of action, whether applied by the patient or professional, or according to their physical and chemical properties. They may be manufactured and delivered in the form of mouthwashes, gels, dentifrices, or agents to be applied topically, such as resin composite, varnishes, glass ionomer cement and periodontal membranes.
The advantage of using products available for home use is that they are immediately available for treatment when compared with those applied by the professional. One disadvantage is that more time is required for remission of symptoms (2–4 weeks), while those applied in-office promote immediate relief.
Fluorides such as sodium and stannous fluoride can reduce DH.15 They precipitate calcium fluoride crystals in the dentinal tubules inlet, creating a barrier. The temporary action of the formed barrier may be due to its slow solubility in saliva. 5 Another fluoride, amine fluoride, has also been used in dentifrice to alleviate dentinal hypersensitivity.16 However, there is little data available on the efficacy of its ability to reduce DH.
Calcium sodium phosphosilicate, a bioactive glass, provides calcium and phosphate ions that form a hydroxycarbonate-apatite, a mineral that is chemically similar to the mineral in enamel and dentine.17 In one of our recent studies, calcium sodium phosphosilicate showed a greater reduction in sensitivity compared to potassium nitrate.18
Considering the aforementioned findings, this study was conducted to assess and compare the efficacy of three commercially available toothpastes containing either 5% potassium nitrate or 5% calcium sodium phosphosilicate or 3.85% amine fluoride compared to a placebo in the reduction of DH over a period of 6 weeks.
Materials and methods
The study was a single centre, longitudinal, triple masked (investigators, subjects and statistician), randomized parallel-arm design. The study duration was 6 weeks, in which sensitivity scores were measured at baseline, at 2 weeks and 6 weeks. The research protocol was initially submitted to the Ethical Committee and Review Board of the Government Dental College and Research Institute, Bangalore, India. After ethical approval, subjects were selected from the outpatient section of the Department of Periodontics, Government Dental College and Research Institute, Bangalore. The duration of the study was from July to October 2011.
The four toothpastes studied were: (1) a commercially available toothpaste containing 5% potassium nitrate (SHY, Group Pharmaceuticals, Mumbai, India); (2) a commercially available non-aqueous toothpaste containing 5% calcium sodium phosphosilicate with fused silica (SHY-NM, Group Pharmaceuticals, Mumbai, India); (3) a commercially available toothpaste containing 3.85% amine fluoride (AMFLOR, Group Pharmaceuticals, Mumbai, India); and (4) a placebo toothpaste (Group Pharmaceuticals, Mumbai, India).
Sample size calculations were based on detecting a difference of 30% reduction in visual analogue scale (VAS) scores19 between test and control groups using a two-tailed significance level of 5% with a 90% power.
A total of 160 subjects were included in the study, randomized and categorized into four groups, each containing 40 subjects. The randomization was done using a computer-generated random table, and investigators were neither involved in the randomization process nor were they aware of the assigned groups. The toothpastes were dispensed in white tubes by the investigator (ARP) labelled A, B, C and D, the contents of which were disclosed to the investigators only after completion of the statistical analyses.
A total of 149 subjects (72 males and 77 females) were finally considered because 11 subjects failed to follow-up or discontinued the treatment.
There were 39 subjects in Group 1, 36 in Group 2, 38 in Group 3 and 37 in Group 4 who finally completed the study. Subjects participating in the study were aged 20 to 60 years. The mean age was not statistically different among groups and ranged from 41.7 years for Group 1, 38.9 years for Group 2, 38.2 years for Group 3 and 40.6 years for Group 4. Subjects who were in good general health, could fulfill the scheduled appointment and gave written informed consent to participate were recruited to the six-week trial. A flow chart of the study is provided in Fig. 1.
Inclusion and exclusion criteria
Volunteers selected at baseline had a history of DH caused by gingival recession or cervical erosion. Patients who had at least two teeth with a VAS score of ≥4 were included in the study. Teeth with caries, defective restorations, occlusal restorations, chipped teeth, deep periodontal pockets (no probing depth >4 mm), periodontal surgery within the previous 6 months, and subjects with orthodontic appliances or bridge work that would interfere with evaluation were excluded. In addition, subjects were also excluded if they were allergic to ingredients used in the study or exhibited any gross oral pathology, eating disorders, chronic disease, pregnancy and lactation, acute myocardial infarction within the past 6 months, use of pacemaker, uncontrolled metabolic disease, major psychiatric disorder, heavy smoking or alcohol abuse, any systemic disease or any disease requiring repeated or regular analgesia, anti-inflammatory drugs, or antihistamines.
To assess tooth sensitivity, a controlled air stimulus (evaporative stimulus) and cold water (thermal stimulus) were used. Sensitivity was measured using a 10 cm VAS score, with a score of zero being a pain-free response and a score of 10 being excruciating pain or discomfort. Scoring of tooth sensitivity was done first by using controlled air pressure from a standard dental syringe at 40 to 65 psi at ambient temperature, directed perpendicularly and at a distance of 1 to 3 mm from the exposed dentine surface while adjacent teeth were protected with gloved fingers to prevent false-positive results.
This was followed by scoring of tooth sensitivity using 10 ml of ice cold water applied to the exposed dentine surface while neighbouring teeth were isolated during testing using the operator’s fingers and cotton rolls. A period of at least 5 minutes was allowed between the two stimuli on each tooth. The types of teeth included in the study are shown in Table 1.
Table 1. Types of teeth included in the study
|Upper central incisor||6.1|
|Upper lateral incisor||5.7|
|Lower central incisor||5.7|
|Lower lateral incisor||2.5|
After recording sensitivity scores at baseline (EA), subjects were randomly given respective toothpastes and advised to use the toothpaste with soft bristle toothbrushing twice a day. Subjects were also directed to refrain from any other dentifrice or mouthrinse during the trial but were allowed to continue their normal oral hygiene practice.
Mean VAS scores and mean ± SD were calculated from raw VAS scores from all subjects in a treatment group. Mean VAS scores were compared among groups at different time points (baseline, at 2 weeks and 6 weeks) and among groups at each time point using one-way analysis of variance (ANOVA). Post hoc pair-wise multiple comparisons were done; p < 0.05 was taken as significant when detected. Data were statistically analysed using a software programme (SPSS statistical package, Version 17.5, SPSS, Chicago, IL, USA).
Mean VAS scores for air stimulus and water stimulus for all four groups at baseline, and at 2 and 6 weeks are shown in Table 2. Group 2 resulted in more improvement at 2 weeks and 6 weeks compared to the other groups (Table 2). Intragroup comparison showed that all groups recorded a significant improvement from baseline to 2 weeks, and from baseline to 6 weeks (Table 3). Table 4 shows the intergroup comparison. No significant difference between groups at baseline was found for both air and water stimulus. For air stimulus, there was a significant difference between Group 1 and 2, Group 2 and 3, and Group 2 and 4 at 2 weeks. Similar results were found for water stimulus at 2 weeks. The differences were significant for all the comparisons between groups except between Group 1 and 3 for both air and water stimulus at 6 weeks.
Table 2. Sensitivity scores to air and water stimulus for all groups at baseline, 2 weeks and 6 weeks
|Air stimulus||Group 1||5.48 ± 0.44||4.25 ± 0.45||2.35 ± 0.46|
|Group 2||5.55 ± 0.34||3.78 ± 0.41||1.88 ± 0.44|
|Group 3||5.46 ± 0.59||4.14 ± 0.59||2.09 ± 0.33|
|Group 4||5.31 ± 0.46||4.23 ± 0.40||3.55 ± 0.42|
|Water stimulus||Group 1||6.82 ± 0.34||5.52 ± 0.34||3.11 ± 0.76|
|Group 2||6.95 ± 0.42||4.74 ± 0.50||2.12 ± 0.36|
|Group 3||6.86 ± 0.48||5.37 ± 0.71||2.96 ± 0.42|
|Group 4||6.29 ± 0.41||5.34 ± 0.40||4.13 ± 0.50|
Table 3. Intragroup comparison of air and water scores between different visits
|Group 1||Baseline – 2 weeks||<0.001*|
|Baseline – 6 weeks||<0.001*|
|Group 2||Baseline – 2 weeks||<0.001*|
|Baseline – 6 weeks||<0.001*|
|Group 3||Baseline – 2 weeks||<0.001*|
|Baseline – 6 weeks||<0.001*|
|Group 4||Baseline – 2 weeks||<0.001*|
|Baseline – 6 weeks||<0.001*|
Table 4. Intergroup comparison of air and water stimulus at baseline, 2 weeks and 6 weeks
|Air stimulus||Group 1–Group 2||0.55||<0.001*||<0.001*|
|Group 1–Group 3||0.89||0.37||0.47|
|Group 1–Group 4||0.17||0.68||<0.001*|
|Group 2–Group 3||0.46||0.003*||<0.05*|
|Group 2–Group 4||0.53||<0.001*||<0.001*|
|Group 3–Group 4||0.23||0.19||<0.001*|
|Water stimulus||Group 1–Group 2||0.23||<0.001*||<0.001*|
|Group 1–Group 3||0.76||0.27||0.15|
|Group 1–Group 4||0.27||0.34||<0.001*|
|Group 2–Group 3||0.37||<0.001*||<0.001*|
|Group 2–Group 4||0.44||<0.001*||<0.001*|
|Group 3–Group 4||0.32||0.87||<0.001*|
DH is one of the most common and painful, and least successfully treated chronic tooth problems. In 1884, Calvo wrote that ‘there is a great need of a medicament, which while lessening the sensitivity, will not impair the vitality of the pulp’. In spite of a considerable amount of research for more more than 100 years, the clinical management of DH is largely empirical.3
This study compared three commercially available dentifrices and a placebo toothpaste. The results demonstrated a reduction in symptoms for all treatment groups from baseline to 2 and 6 weeks for both measures of sensitivity. There was a remarkable pattern toward reduction of DH with time for all the variables during the 6 weeks of the active phase of the study independent of treatment groups. The calcium sodium phosphosilicate group showed a higher degree of effectiveness at reducing DH than commercially available potassium nitrate and amine fluoride dentifrices and a placebo for both sensitivity measures. There was no statistically significant difference between the results of the potassium nitrate toothpaste and the amine fluoride toothpaste in the reduction of symptoms at the end of 6 weeks.
Well-designed clinical trials providing evidence for the formulation containing all potential active ingredients used in this study can be found in the literature.
The 5% potassium nitrate toothpaste was used as a positive control in our study because it has proved to be clinically efficient in the treatment of DH. Some studies have reported the effectiveness of 5% potassium nitrate gel as an active ingredient.20–22 Unlike other products, potassium nitrate does not diminish dentine hydraulic conductivity, or promote obstruction of dentinal tubules by the deposition of crystals. According to Wilchgers and Ermert23 and Kim,24 the desensitizing effect of potassium nitrate is due to the increase in concentration of extracellular potassium around the nerve fibres which cause their depolarization, avoids repolarization and blocks the axonic action. This blocks the passage of nerve stimulus, resulting in inactivation of the action potential.
Calcium sodium phosphosilicate, originally developed as a regenerative bone material, has been shown to be effective at physically occluding dentinal tubules.17,25 Clinical evaluations of calcium sodium phosphosilicate for the treatment of DH have recorded statistically significant and clinically positive results.18,26 It has been shown that the innovative bioactive glass-containing toothpaste occludes dentinal tubules and resists acid challenge.27,28 Moreover, it has demonstrated a strong antimicrobial behaviour in vitro,29 which reduces symptoms of DH by preventing bacteria to induce pulpal response.
Fluorides such as sodium and stannous fluoride reduce DH.15 The application of fluorides seems to deposit calcium fluoride crystals which form a barrier at the inlet of dentinal tubules. High level fluoride products, such as varnishes, form calcium fluoride which can occlude dentine tubules and provide relief from sensitivity. However, low fluoride products, such as dentifrices and mouthwashes, do not provide significant sensitivity relief. In contrast, stannous fluoride works by depositing insoluble stannous compounds that also occlude tubules to provide sensitivity relief. Amine fluoride has also been used in dentifrice to alleviate dentinal hypersensitivity.16 A mouthrinse based on fluoride salts (potassium fluoride and amine fluoride) has been evaluated for the treatment of dental hypersensitivity and was found to be effective.30 Like calcium sodium phosphosilicate, amine fluoride has been shown to have an antimicrobial affect which may contribute to reducing symptoms of DH by preventing bacteria from inducing a response from the pulp.31
Although 8 weeks was considered a suitable duration for most clinical trials evaluating the efficacy of desensitizing toothpaste, some studies have stated that the optimum time course for different agents differs based on their action. The duration of our study was 6 weeks with sensitivity measured at baseline, at 2 weeks and 6 weeks based on a previous clinical trial conducted for assessment of calcium sodium phosphosilicate as a desensitizing agent.32 Dentine sensitivity may differ for different stimuli,33 and it is recommended that at least two hydrodynamic stimuli be used in the clinical trial. We used evaporative air stimulus and cold water in our study because these are both physiologic and controllable. Evaporative air stimulus was first used for sensitivity assessment followed by water stimuli because the least severe stimulus should be applied first to prevent interpretation error. An interval of ≥5 minutes was allowed between the two stimuli to minimize interactions between stimuli.
In the present study, the placebo group also reported greater reduction in mean sensitivity scores over time. One probable factor may be the environment under which this study was performed. The patients knowingly participated in a clinical trial to determine the efficacy of desensitizing products. Despite randomization and stratification effects to homogenize sample characteristics and their distribution to different groups, enrolled volunteers often try to impress the investigators. Furthermore, positive emotional and motivational behavioural responses during the clinical trial can activate the body’s central pain-inhibiting system.34 The placebo effect, which is the phenomenon of patients reporting relief without using any active ingredient varies from 20% to 60% in DH clinical trials.35,36 The Hawthorne effect can also be responsible for the same. Subjects may show improved oral hygiene due to frequent examinations. Improved oral hygiene would cause more saliva to penetrate dentinal tubules, increasing the deposition of calcium and phosphate and thus decreasing the pain sensation. The influence of the Hawthorne effect is difficult to calculate.
A study of Australian dentists found that most had a sound knowledge of the current mechanisms underlying dentinal hypersensitivity The most common management strategy employed was to prescribe desensitizing agents for home use.37
In agreement with other studies, statistically significant positive placebo responses can be expected in DH treatment studies which may mask the positive treatment effects of active ingredients. To prevent the placebo effect which may mask the treatment affects of an effective agent, the design of the clinical trials done for DH should be modified and improved.
After 6 weeks of clinical evaluation, all treatments showed lower VAS sensitivity values compared with baseline, independent of their different modes of action. Under clinical trial conditions, the calcium sodium phosphosilicate group showed better results compared to a fluoride or a potassium nitrate dentifrice in reducing DH symptoms. Further, well-designed, multicentre, prospective, long-term clinical trials with scanning electron microscope evaluations should be undertaken to find the gold standard treatment of DH.
The authors express their gratitude to Mr R Pacheiyappan, Manager–Sales and Marketing, Group Pharmaceuticals, Bangalore, India, for his support in providing SHY-NM (calcium sodium phosphosilicate), SHY (potassium nitrate), AMFLOR (amine fluoride) and the placebo pastes. The authors also express their thanks to Mr BS Nandakumar and his team for carrying out all the required statistics. The authors report no conflicts of interest related to this study.