|Year : 2021 | Volume
| Issue : 1 | Page : 24-30
Clinical efficacy of single application of plain nano-hydroxyapatite paste in reducing dentine hypersensitivity - A randomized clinical trial
Dalia N Alharith1, Mohammad Al-Omari1, Raid Almnea2, Rabea Basri3, Asma H Alshehri3, Atheel Ahmad Al-Nufiee3
1 Department of Restorative Dentistry-Division of Endodontics, College of Dentistry, Riyadh Elm University, Riyadh, Saudi Arabia
2 Department of Restorative Dentistry-Division of Endodontics, College of Dentistry, Najran University, Najran, Saudi Arabia
3 General Dentist, College of Dentistry, Riyadh Elm University, Riyadh, Saudi Arabia
|Date of Submission||11-Mar-2020|
|Date of Decision||26-Mar-2020|
|Date of Acceptance||15-Apr-2020|
|Date of Web Publication||09-Jan-2021|
Dr. Dalia N Alharith
Department of Restorative Dentistry.Endodontics, College of Dentistry, Riyadh Elm University, P.O. Box: 84891, Riyadh 11681
Source of Support: None, Conflict of Interest: None
Introduction: The study aimed to compare the efficacy of a single application of plain nano-hydroxyapatite (n-HA) paste in reducing dentine hypersensitivity.
Materials and Methods: Sixty-three patients were recruited to participate in the study and randomized to be allocated into three groups (n-21): (1) Group 1 – n-HA paste, (2) Group 2 – fluoride paste, and (3) Group 3 – placebo. The patient's response to dentin hypersensitivity (DH) was evaluated at baseline (T0), immediately after application (T1), and after 1 week (T2). Tactile and cold air sensitivity (CAS) stimulus tests and visual analog scale subjective tests were used to measure the patient's response to DH. The data analysis was performed using the Statistical Package for the Social Sciences statistical software.
Results: All three groups showed a statistically significant reduction in tactile sensitivity (TS), cold air sensitivity, and visual analog scale scores from T0–T1 and T0–T2 (P < 0.005). However, from T1–T2, there was no significant reduction in the TS, cold air sensitivity, and visual analog scale scores of the groups (P > 0.005) except for Group 1, which showed a significant reduction (P = 0.033) in visual analog scale scores from T1–T2. However, the intergroup comparison at T2 demonstrated a significant difference in tactile scores (P = 0.005), CAS (P < 0.001), and visual analog scale scores (P < 0.001). There was no incidence of treatment-related adverse events with the study products.
Conclusion: n-HA paste was the most effective desensitizing paste compared to fluoride and placebo pastes. The single application of the n-HA paste demonstrated a significant reduction in visual analog scale scores after 1-week.
Keywords: Cold air, dentine hypersensitivity, fluoride, hydroxyapatite, tactile tests, visual analog scale
|How to cite this article:|
Alharith DN, Al-Omari M, Almnea R, Basri R, Alshehri AH, Al-Nufiee AA. Clinical efficacy of single application of plain nano-hydroxyapatite paste in reducing dentine hypersensitivity - A randomized clinical trial. Saudi Endod J 2021;11:24-30
|How to cite this URL:|
Alharith DN, Al-Omari M, Almnea R, Basri R, Alshehri AH, Al-Nufiee AA. Clinical efficacy of single application of plain nano-hydroxyapatite paste in reducing dentine hypersensitivity - A randomized clinical trial. Saudi Endod J [serial online] 2021 [cited 2021 Jun 13];11:24-30. Available from: https://www.saudiendodj.com/text.asp?2021/11/1/24/306612
| Introduction|| |
Dentin hypersensitivity (DH) is one of the most frequently encountered patient complaints in dental practice, and the frequency ranges from 4.8% to 62.3%., DH is characterized by sharp, localized pain of short duration and is found to greatly affect the patients' quality of life. The major etiologies of DH are gingival recession, aging problems, and periodontal care such as scaling and root planing in addition to improper teeth brushing. The DH is best explained by Brannstrom's hydrodynamic theory which suggests that certain external stimuli may induce fluid movement within the dentinal tubules that stimulate the nerve endings, thereby causing pain. Consequently, any materials or techniques that reduce the movement of dentinal fluid are found to reduce DH.
The treatment strategies for DH include chemical and/or mechanical occlusion or masking of dentine tubules. This is accomplished by fluoride varnishes, potassium nitrate, calcium silicate, strontium chloride, sodium monofluorophosphate, dentine bonding agents, resin composites, lasers, and periodontal soft-tissue graft.,
The application of nanomaterials for diagnosis, treatment, and drug delivery in the medical field is well established. However, their use in dentistry (nanodentistry) is gaining momentum from the previous decade. Nanoparticles (NPs) include nanoscale spherical, cubic, and needle-like particles (about 5–100 nm), and the resulting properties of the materials are significantly enhanced with the inclusion of NPs. It was said that NPs also tend to be highly effective in managing pain associated with dentine hypersensitivity. The NP size and reactivity plays an important role in allowing them to be distributed in the dentine tubules with improved decontamination, enhanced remineralization, and decreased sensitivity compared to conventional treatment regimens. Furthermore, the large surface area and high surface energy significantly contribute to the solubility and reactivity of NPs.
The use of fluorides for remineralization of teeth dates back to the mid-20th century. They have been incorporated to toothpaste in the form of sodium monofluorophosphate or stannous fluoride. They are primarily used for preventing or treating dental caries and have also been used for the treatment of DH. However, the emphasis on the inorganic mineral portion (calcium and phosphate) of the tooth structure has encouraged the development of hydroxyapatite (HA) for the treatment of DH. The use of different forms of HA for occluding dentin tubules has found a promising outcome.
In recent years, the application of nanotechnology has led to the development of nano-HA (n-HA) particles. In terms of morphology and crystal composition, nano-sized HA particles resemble the apatite crystals of the tooth enamel and are studied as biomimetic materials due to their potential as the remineralizing agent. n-HA has been successfully used to treat bleaching-related hypersensitive teeth and also has been reported to reduce DH by occluding the exposed dentinal tubules.,,,, However, the previous studies have studied that n-HA pastes which are blended with fluoride, potassium nitrate, or other ingredients were used as toothpaste. In such a situation, the limitations would be to determine the actual constituents which could reduce DH.
Consequently, the study aimed to assess the short-term efficacy of a single in-office application of plain n-HA paste in reducing dentin hypersensitivity and to compare the outcome with that of a commercially available fluoride and placebo paste.
| Materials and Methods|| |
Ethical aspects and participants enrollment
The study was conducted as per the ethical principles adopted at the Helsinki Declaration. The Institutional Review Board (IRB) of the Riyadh Elm University-College of Dentistry approved this study (RC/IRB/2016/112). The study is registered (NCT02936830) with the clinical trial register at (https://clinicaltrials.gov/). The present study is reported as per the Consolidated Reporting Trial Standards and good clinical practice guidelines. Participation in the study was voluntary, and the recruited participants were explained about the purpose, duration, and procedures of the study. Informed consent was obtained from patients who were willing to participate in the study.
Sample size calculation
G * Power v. 22.214.171.124 software (Heinrich-Heine-Universität Düsseldorf, Germany) was used to calculate the sample size for this study. A statistical power of 85%, an error margin of 10% with effect size measurement (f) at 40% was applied for the calculation. A total of 60 subjects (20 × 3 groups = 60 subjects) were required for the study.
The study was conducted at the outpatient clinics of Riyadh Elm University-College of Dentistry, Riyadh, Saudi Arabia from October to December (2016). A total of 79 healthy adult patients aged between 18 and 60 years were evaluated, of which 63 of them were included in this study based on the inclusion and exclusion criteria.
The inclusion criteria were hypersensitive areas on facial surfaces of the teeth (incisors, canines, premolars, and first molars with exposed cervical dentin) with at least two teeth scoring “pain (scores 2 and 3 on scale stimuli test)” during the application of stimulus (air blast and tactile sensitivity [TS] test), good periodontal health (probing depth < 4 mm) with no other conditions that might explain their apparent dentin hypersensitivity, and good overall physical health with provision of written informed consent.
Exclusion criteria were chipped teeth, defective restorations, fractured undisplaced canines, deep dental caries or periodontal pockets, orthodontic appliances, dentures or fixed dental prostheses that would interfere with the evaluation of hypersensitivity, periodontal surgery within the previous six months, ongoing treatment with antibiotics and/or anti-inflammatory drugs or for tooth hypersensitivity, pregnancy or lactation, heavy smokers, and alcohol or drug abuse.
The initial visit/screening form was filled for all the patients after obtaining a detailed case history. The enrolled patients were randomly allocated to either of the three groups.
- Group 1: NanoXIM® n-HA paste (15% plain n-HA, FLUIDINOVA, S. A., Moreira da Maia, Portugal)
- Group 2: Fluoraphat Pro® paste (Sodium fluoride (NaF) 5%, Promedica Dental Material GmbH, Neumünster, Germany)
- Group 3: : Placebo (Glycerin, water, Ivory Med Company, Riyadh, Kingdom of Saudi Arabia)
Following inclusion, all the patients underwent thorough oral prophylaxis and were educated about using visual analog scale (VAS) through a training exercise. The patients were instructed to refrain from using any kind of desensitizing toothpaste, mouth rinses, and analgesics for at least 2 weeks before the study and also for the remainder of the study period.
Randomization and examiner blinding
Randomization for group allocation was performed using a computer-generated list (https://www.randomizer.org) and each patient received a unique identification code. An independent faculty who was blinded to the study design and procedures performed randomization and group allocation. The test materials were overwrapped by other faculty members at a different area away from the clinical site and were kept in identical boxes and named accordingly as A, B, and C. Both the patients and examiners were blinded to the study design and outcome assessment.
The eligibility for the patient's inclusion was assessed using stimuli tests (TS and cold air sensitivity [CAS] and VAS) response measures which are described below.
- TS: A sharp dental explorer with a constant force was gently passed on the affected area, perpendicular to the long axis of the tooth
- CAS: Prior to the CAS test, the sensitive area of the teeth was mechanically cleansed by cotton swab soaked in distilled water. In this test, compressed cold air from a three-way air syringe at 72 (±5) psi was aimed perpendicular to the exposed dentin surface from a distance of about 1 cm for 1 s. The teeth adjacent to the test teeth were isolated using cotton rolls, and the patient's response to the stimulation was recorded on a 100 mm VAS
- Examiner assessment?(Schiff sensitivity scale [SSS]): Before the patients recorded their response to the air stimulus on the VAS, the sensitivity was determined by the examiner using the SSS scores. The scoring criteria are as follows: 0 – a patient does not react to the stimulus; 1 – a patients react to stimulus but does not request discontinuation of stimulus; 2 – a patient reacts to stimulus and requests discontinuation or moves from stimulus; and 3 – a patient reacts to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. The increased level of DH was determined by high SSS scores. The patients were included in the study if the score was 2 or 3 on the SSS. All the tests were performed in a sequence with a 5-min interval between the tests.
The assessments were performed before (T0) and after (T1) study product application at the baseline visit and 1-week follow-up visit (T2). The assessment was performed by the principal investigator and a trained clinician, both of whom were fully blinded during the entire study. The calibration of the examiners was performed on three random patients who were recruited for the study. The examiners were trained and calibrated by a principal investigator on DH response measurement techniques. The interexaminer agreement was evaluated using the kappa (κ) statistic.
Oral application of study products
Polishing was done on the designated hypersensitive teeth with a clinical prophylaxis brush without polishing paste before the application of the study products. Following polishing, the patients with at least two sensitive teeth received treatment with either of the study products (either A, B, or C). The principal investigator and the trained clinician responsible for applying the tested materials performed the application procedures. A disposable cotton bud was used for the application of the study pastes for each patient. The pastes were applied at the gingivofacial one-third of each designated tooth for 5 min. The procedure of application remained identical for all the study products. Following the application, the T1 was performed.
At the 1-week follow-up visit, T2 was performed, and the patients in all the three groups then received the nano-XIM care paste to ensure that all patients received treatment with the test product. In addition, the patients were examined for any adverse reactions with the application of the study products.
The data analysis was performed using the Statistical Package for the Social Sciences statistical software (version 21, IBM Corp, Chicago, USA). The Shapiro–Wilk test was applied to assess the normality of distribution. Descriptive statistics were calculated for TS, CAS, and VAS scores at different periods. The differences in the scores between each group at different periods were assessed by Wilcoxon signed-rank tests. Kruskal–Wallis test was applied to determine the mean difference in TS, CAS, and VAS scores among the test materials. Independent Mann–Whitney U-tests were applied to determine the mean difference between the two test materials. “P” = 0.05 was considered significant for all analyses.
| Results|| |
A total of 79 patients were screened for the study, of which 16 were excluded from the study. Among the excluded patients, 13 did not meet the inclusion criteria and three declined to participate in the study. The 63 patients (45 female and 18 male) included were randomly allocated into three groups (n = 21) [Figure 1]. The mean age of the patients was 39 years.
The mean interexaminer reliability values for the sensitivity measurements comparing the principal investigator versus each of the two examiners were 0.76 and 0.79. This outcome agreed with the acceptability target set for training and calibration.
The Shapiro–Wilk test showed that the data were not normally distributed (P < 0.05). [Table 1] presents the TS, CAS, and VAS test scores of the groups at different periods. All the study products showed a statistically significant reduction in TS, CAS, and VAS scores from T0–T1 and T0–T2 (P < 0.005). However, from T1–T2, there was no significant reduction in the TS, CAS, and VAS scores of the groups (P > 0.005) except for the n-HA group, which showed a significant reduction (P = 0.033) in VAS scores from T1–T2.
|Table 1: Mean tactile sensitivity, cold air sensitivity and visual analogue scale test scores of the groups|
Click here to view
The highest mean reduction in TS, CAS, and VAS scores from T0–T1 was observed with the placebo paste, followed by n-HA and fluoride paste. From T0–T2, the highest mean difference in the test scores was observed with the n-HA paste, followed by fluoride and placebo pastes. However, the placebo paste showed an increased TS (0.29), CAS (0.43), and VAS (10.71) scores from T1–T2, and the n-HA and fluoride paste showed a decreased TS, CAS, and VAS scores [Figure 2].
|Figure 2: Mean reduction in the measured parameters between the groups at different periods. (a) Tactile sensitivity (TS), (b) cold air sensitivity (CAS) and c) Visual analogue scale (VAS)|
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The intergroup comparison of the scores at different periods is presented in [Table 2]. The fluoride, n-HA, and placebo pastes did not yield any significant difference in mean TS, CAS, and VAS scores at T0 and T1. However, the intergroup comparison at T2 demonstrated a significant difference in TS (P = 0.005), CAS (P = 0.001), and VAS scores (P < 0.001).
There was no reported incidence of treatment-related adverse events (such as allergy or hypersensitivity) with any of the study products at the 1-week examination.
| Discussion|| |
This clinical trial was designed as a single site, randomized, double-blind, three-arm parallel-group study of subjects with hypersensitive teeth in accordance with the criteria set forth by Vano et al. The enrolled patients had at least two hypersensitive teeth that met the tactile and air blast hypersensitivity enrolment criteria and were, therefore, eligible to participate in the study. The enrollment criteria applied in the current study were consistent with the accepted diagnosis of dentin hypersensitivity., The study was conducted over 1 week period and comprised a baseline and immediate examination followed by a recall visit after 1 week.
In this study, we investigated the efficacy of a test paste containing 15% n-HA in reducing or eliminating the acute complaints of DH in a single application with a 1-week follow-up. It was important for a follow-up to determine which study materials would provide long-term relief from DH. This is because the slow onset action of desensitizing agents is considered disadvantageous; therefore, research is focused on investigating the efficacy of immediate pain relief products in alleviating the pain symptoms of DH. This is the first study till date to evaluate the short-term efficacy of n-HA in its purest form without any additives such as potassium nitrate or fluoride. The results showed a significant reduction in DH for the n-HA group for TS, CAS, and subjective evaluation using VAS at T1 and T2. A single application of 15% nano-XIM paste provided quick and sustained relief from symptoms as compared to other study products. This could be beneficial for the patients visiting the dental office with the complaint of DH. The patient could be immediately relieved of the pain, and it would also allow the clinician to plan for a definitive treatment for DH.
n-HA is considered one of the most biocompatible, and as previous studies have shown, is more effective than fluoride. n-HA promotes surface remineralization forming an instant biomimetic apatite coating on enamel and dentin surfaces due to the chemical–physical characteristics of the n-HA particles that closely resemble enamel mineral constituents.
According to the previous studies evaluating the effect of n-HA, it has been stated that n-HA occludes the dentinal tubules thereby causing progressive closure of the tubular openings.,, Another important function of n-HA is the regeneration of the mineralized layer that enhances the desensitizing action of the applied paste, which also explains the significant decrease of DH 1-week postapplication in this study. Furthermore, the effectiveness of n-HA is also determined by the concentration of the NPs. Shetty et al. found an enhanced desensitizing action with 100% n-HA as compared with 25%, and the authors concluded that higher NP concentration increases the penetration of the particles into the tubules.
Most hypersensitive teeth are sensitive to more than one stimuli but not all teeth respond to the same stimulus. Accordingly, the tooth sensitivity in this study was measured by more than one stimulus, TS, and CAS tests as recommended by Holland et al. The level of tooth sensitivity response was determined by translating the subjective feedback scale into objective data using a VAS. The validity and reliability of a VAS for measuring both experimental and clinical pain are well established. In the present study, VAS scores were recorded at T0, T1, and T2 after the paste application. A statistically significant difference was found at both T1 and T2 following application of the n-HA test paste which is in agreement with the outcome of the previous study.
In this study, all the patients moved away from the stimulus or requested immediate discontinuation (SSS 2 or 3) when the cold air stimulus was applied. Following n-HA paste application, the patients did not respond to the stimulus (SSS score 0 or 1) and the relief was maintained without further application of the paste which is contradictory to the outcome of the previous studies. Also, the TS score in this study was much lower compared to the previous study by Ayad et al. These differences could be explained by the low baseline scores for tactile hypersensitivity in the current study. Many participants did not respond to TS, even if CAS reached high score.
In the current study, positive control group (5% sodium fluoride) and a placebo group was used to provide a baseline value against which the effectiveness of the active treatment group could be measured. The fluoride paste did provide an immediate significant reduction in DH but did not show any significant difference in VAS score which is similar to the findings of a previous study. In spite of the psychological effects that arise in reaction to placebo therapies, the placebo group received a significant reduction in DH following immediate application. Chronic pain, insomnia, and decreased motor function are the pathologic conditions that are most affected by the placebo effect.
The lack of clinical effects in this investigation's placebo group can be explained by the acute and temporary nature of the pain that characterizes DH and the positive changes in patient behavior during the study (Hawthorne effect). The context in which the medical treatment is carried out plays an important role in the outcome of treatment. The context of treatment such as doctors, nurses, hospitals, syringes, and pills can influence the patient's perception of properly assessing the outcome of placebo therapy, thereby influencing the outcome of treatment.
This study had some strengths and limitations. Accurate assessment of test scores and double-blind randomization are the strength, whereas the small sample size and short-term follow-up are the study limitations. Further long-term studies are required to evaluate the treatment outcome of such paste in managing DH. Furthermore, the inclusion of a wash-out period, interchanging of the groups, and larger sample size may present with more actual information on the clinical use of n-HA paste.
| Conclusion|| |
Within the limitations of the study, n-HA paste was the most effective desensitizing paste compared to fluoride and placebo pastes. The single application of the n-HA paste demonstrated a significant reduction in visual analog pain scores after 1-week.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Janani K, Ajitha P, Sandhya R. Improved quality of life in patients with dentin hypersensitivity. Saudi Endod J 2020;10:81-2. [Full text]
Kripal K, Chandrasekaran K, Chandrasekaran S, Kumar VR, Chavan SK, Dileep A. Treatment of dentinal hypersensitivity using propolis varnish: A scanning electron microscope study. Indian J Dent Res 2019;30:249-53.
] [Full text]
Aghanashini S, Puvvalla B, Nadiger S, Mundinamanae D, Bhat D, Andavarapu S. Comparative evaluation of diode laser and fluoride varnish for treatment of dentin hypersensitivity: A clinical study. J Interdiscip Dent 2018;8:110-17.
Matthews B, Vongsavan N. Interactions between neural and hydrodynamic mechanisms in dentine and pulp. Arch Oral Biol 1994;39 Suppl: 87S-95S.
Markowitz K, Pashley DH. Personal reflections on a sensitive subject. J Dent Res 2007;86:292-5.
Gopinath NM, John J, Nagappan N, Prabhu S, Kumar ES. Evaluation of dentifrice containing nano-hydroxyapatite for dentinal hypersensitivity: A randomized controlled trial. J Int Oral Health 2015;7:118-22.
Cushing BL, Kolesnichenko VL, O'Connor CJ. Recent advances in the liquid-phase syntheses of inorganic nanoparticles. Chem Rev 2004;104:3893-946.
Besinis A, De Peralta T, Tredwin CJ, Handy RD. Review of nanomaterials in dentistry: Interactions with the oral microenvironment, clinical applications, hazards, and benefits. ACS Nano 2015;9:2255-89.
Onwubu S, Mdluli P, Singh S. The effectiveness of nanomaterials in the management of dentine hypersensitivity-a review. J Clin Rev Case Rep 2018;3:1-5.
Low S, Allen EP, Kontogiorgos ED. Reduction in dental hypersensitivity with nano-hydroxyapatite, potassium nitrate, sodium monoflurophosphate and antioxidants. Open Dent J 2015;9:92-7.
Hannig M, Hannig C. Nanomaterials in preventive dentistry. Nat Nanotechnol 2010;5:565-9.
Browning WD, Cho SD, Deschepper EJ. Effect of a nano-hydroxyapatite paste on bleaching-related tooth sensitivity. J Esthet Restor Dent 2012;24:268-76.
Anand S, Rejula F, Sam JV, Christaline R, Nair MG, Dinakaran S. Comparative evaluation of effect of nano-hydroxyapatite and 8% arginine containing toothpastes in managing dentin hypersensitivity: Double blind randomized clinical trial. Acta Medica (Hradec Kralove) 2017;60:114-9.
Vano M, Derchi G, Barone A, Covani U. Effectiveness of nano-hydroxyapatite toothpaste in reducing dentin hypersensitivity: A double-blind randomized controlled trial. Quintessence Int 2014;45:703-11.
Kunam D, Manimaran S, Sampath V, Sekar M. Evaluation of dentinal tubule occlusion and depth of penetration of nano-hydroxyapatite derived from chicken eggshell powder with and without addition of sodium fluoride: An in vitro
study. J Conserv Dent 2016;19:239-44.
] [Full text]
Mason S, Kingston R, Shneyer L, Harding M. Clinical study to monitor dentinal hypersensitivity with episodic use of a desensitising dentifrice. BDJ Open 2017;3:17011.
Canadian Advisory Board on Dentin Hypersensitivity. Consensus-based recommendations for the diagnosis and management of dentin hypersensitivity. J Can Dent Assoc 2003;69:221-6.
Holland GR, Narhi MN, Addy M, Gangarosa L, Orchardson R. Guidelines for the design and conduct of clinical trials on dentine hypersensitivity. J Clin Periodontol 1997;24:808-13.
Al-Sabbagh M, Brown A, Thomas MV. In-office treatment of dentinal hypersensitivity. Dent Clin North Am 2009;53:47-60, viii.
Roveri N, Battistella E, Bianchi C, Foltran I, Foresti E, Iafisco M, et al
. Surface enamel remineralization: Biomimetic apatite nanocrystals and fluoride ions different effects. J Nanomater 2009;2009: Article ID 746383, 1-9.
Lee SY, Kwon HK, Kim BI. Effect of dentinal tubule occlusion by dentifrice containing nano-carbonate apatite. J Oral Rehabil 2008;35:847-53.
Najibfard K, Ramalingam K, Chedjieu I, Amaechi BT. Remineralization of early caries by a nano-hydroxyapatite dentifrice. J Clin Dent 2011;22:139-43.
Wang L, Magalhães AC, Francisconi-Dos-Rios LF, Calabria MP, Araújo D, Buzalaf M, et al
. Treatment of dentin hypersensitivity using nano-hydroxyapatite pastes: A randomized three-month clinical trial. Oper Dent 2016;41:E93-101.
Shetty S, Kohad R, Yeltiwar R. Hydroxyapatite as an in-office agent for tooth hypersensitivity: A clinical and scanning electron microscopic study. J Periodontol 2010;81:1781-9.
Trowbridge HO, Silver DR. A review of current approaches to in-office management of tooth hypersensitivity. Dent Clin North Am 1990;34:561-81.
Clark GE, Troullos ES. Designing hypersensitivity clinical studies. Dent Clin North Am 1990;34:531-44.
Jena A, Shashirekha G. Comparison of efficacy of three different desensitizing agents for in-office relief of dentin hypersensitivity: A 4 weeks clinical study. J Conserv Dent 2015;18:389-93.
] [Full text]
Fu Y, Li X, Que K, Wang M, Hu D, Mateo LR, et al
. Instant dentin hypersensitivity relief of a new desensitizing dentifrice containing 8.0% arginine, a high cleaning calcium carbonate system and 1450 ppm fluoride: A 3-day clinical study in Chengdu, China. Am J Dent 2010;23 Spec No A: 20A-27A.
Ayad F, Ayad N, Zhang YP, DeVizio W, Cummins D, Mateo LR. Comparing the efficacy in reducing dentin hypersensitivity of a new toothpaste containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride to a commercial sensitive toothpaste containing 2% potassium ion: An eight-week clinical study on Canadian adults. J Clin Dent 2009;20:10-6.
Colloca L, Benedetti F. Placebos and painkillers: Is mind as real as matter? Nat Rev Neurosci 2005;6:545-52.
McCarney R, Warner J, Iliffe S, van Haselen R, Griffin M, Fisher P. The Hawthorne Effect: A randomised, controlled trial. BMC Med Res Methodol 2007;7:30.
Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context effects on health outcomes: A systematic review. Lancet 2001;357:757-62.
[Figure 1], [Figure 2]
[Table 1], [Table 2]