Neurosensory analysis of tooth sensitivity during at-home dental bleaching: a randomized clinical trial

Abstract Objective The objective of this study was to evaluate dental sensitivity using visual analogue scale, a Computerized Visual Analogue Scale (CoVAS) and a neurosensory analyzer (TSA II) during at-home bleaching with 10% carbamide peroxide, with and without potassium oxalate. Materials and Methods Power Bleaching 10% containing potassium oxalate was used on one maxillary hemi-arch of the 25 volunteers, and Opalescence 10% was used on the opposite hemi-arch. Bleaching agents were used daily for 3 weeks. Analysis was performed before treatment, 24 hours later, 7, 14, and 21 days after the start of the treatment, and 7 days after its conclusion. The spontaneous tooth sensitivity was evaluated using the visual analogue scale and the sensitivity caused by a continuous 0°C stimulus was analyzed using CoVAS. The cold sensation threshold was also analyzed using the TSA II. The temperatures obtained were statistically analyzed using ANOVA and Tukey's test (α=5%). Results The data obtained with the other methods were also analyzed. 24 hours, 7 and 14 days before the beginning of the treatment, over 20% of the teeth presented spontaneous sensitivity, the normal condition was restored after the end of the treatment. Regarding the cold sensation temperatures, both products sensitized the teeth (p<0.05) and no differences were detected between the products in each period (p>0.05). In addition, when they were compared using CoVAS, Power Bleaching caused the highest levels of sensitivity in all study periods, with the exception of the 14th day of treatment. Conclusion We concluded that the bleaching treatment sensitized the teeth and the product with potassium oxalate was not able to modulate tooth sensitivity.


Introduction
At-home bleaching technique is recognized as a simple, biologically safe, and aesthetically effective therapy 4,10,17 . Studies established that reactive forms of oxygen promote oxidation of pigments, giving teeth a lighter appearance 10 . Upon penetrating the dental tissues, they quickly diffuse in the dental tissues reaching the chemosensitive ion channel (TRPA1), this activates the intradental nerves, causing discomfort 18,19 . Post-bleaching sensitivity was also related to the morphological changes that presumably alter the permeability, resulting in temporary sensitivity after the procedure 5,20 .
For this reason, products that repair these superficial changes are continually added in the composition of the bleaching agent 5 , blocking dentin tubules 2,5,6 , or acting in the transmission of nerve impulses, decreasing the ability of nerve fibers in the dental pulp to repolarize after an initial depolarization due to pain sensation 2 .
Some researchers verified that oxalates form crystals in the dental tissue and cause substantial changes in the dentinal fluid flow, reducing pain 11 . On the other hand, a systematic review by Cunha-Cruz, et al. 7  The TSA II-NeuroSensory Analyzer (Medoc; Ramat Yishai, Northern District, Israel) equipment has been used to quantify neurosensory responses from the larger and smaller fibers through provoked thermal stimuli, allowing the temperature that gives discomfort to the patient to be detected, this is an important information for studies on sensitivity 13,21 . This device has a central unit that generates and emits thermal stimuli through an intraoral probe. The patient holds a control device that stops the stimulus as soon as it is detected and the temperature at that moment is registered by the computer software. Thus, it is an interesting tool to analyze the discomfort felt by patients exposed to daily thermal stimuli. The accuracy of the method was highlighted by Gillam, et al. 11 (2004), who revealed its efficiency when compared to other tests in a study of dental hypersensitivity.
Considering that dental sensitivity is the most common side effect after bleaching, a detailed study of its occurrence and intensity is important to establish comfortable therapies. This study aimed to evaluate the occurrence of spontaneous dental sensitivity and tooth sensitivity to cold produced through a thermal stimulus during and after whitening with carbamide peroxide, with or without oxalate.
The hypotheses tested were: (1) dental bleaching performed with carbamide peroxide with potassium oxalate added would reduce the intensity of spontaneous dental sensitivity, and (2)  and 21 days after the beginning of the treatment, as well as 7 days after the conclusion of the treatment.
Sample size was calculated for superiority trial, because we wanted to detect if one bleaching product would be more effective in reducing the intensity of the tooth sensitivity than the other. Furthermore, we considered the outcome intensity of tooth sensitivity for the sample size calculation and the variation used for this purpose was 5%.
We used a statistics calculator and it was considered the type-I error rate (α=5%) -the probability of finding a difference when a difference does not exist; type-II error rate (β=20%) -the probability of not detecting a difference when one actually exists, a 5% Neurosensory analysis of tooth sensitivity during at-home dental bleaching: a randomized clinical trial J Appl Oral Sci. 2018;26:e20170284 3/8 level of significance, which means that the chance of the finding being true is 95%; and a power of the test of 80%, which means that, if indeed there is any difference, the probability of detecting it will be 80%.
Thus, the minimal sample size required was 10.

Inclusion and exclusion criteria
The volunteers were healthy individuals between and received a syringe of each product, which was applied daily for 4 h over the following three weeks.
They were also instructed to use the trays during the afternoon, and to avoid brushing the teeth before that.

Results
Thirty patients were recruited for the study, but five did not meet the pre-determined inclusion criteria.
Thus, 25 volunteers received the proposed treatment and were included in the analysis performed. No losses were verified for the study groups (Figure 3).

Spontaneous tooth sensitivity
The spontaneous sensitivity analysis showed that in most cases, the volunteers presented no discomfort during treatment. Thus, 6 patients (24%) had tooth sensitivity 24 hours before using the product Power Bleaching 10% (T2), 10 patients (40%) presented the discomfort 7 days after treatment initiation (T3) and after 14 days (T4), 8 patients (32%) reported sensitivity. On the other hand, 7 (28%), 6 (24%) and 7 (28%) patients in T2, T3 and T4, respectively, presented the discomfort using the product Opalescence 10% Patients using Power Bleaching 10% mainly reported sensitivity 7 days after starting the treatment, mostly at a low-level, however, scores similar to the baseline were restored after the end of the treatment, with no volunteers presenting tooth sensitivity in both groups (T5; Figure 4).

Dental cold sensation threshold
We applied the Tukey test to compare the performance of both bleaching materials. We verified that both products sensitized the teeth (p<0.05) and no significant differences were detected between the bleaching products in the six study periods (p>0.05).
Thus, emphasizing that the higher the temperature, the more sensitive the tooth was, is important (Table 1).

Computerized Visual Analogue Scale (CoVAS)
Dental sensitivity in both study groups was observed on all study periods when a continuous thermal stimulus (0ºC) was applied (CoVAS test). Lastly, we note that although color alteration was not analyzed in our study, both bleaching products used Other authors have reported that the penetration of hydrogen peroxide from the bleaching agents promote the activation of the ion channel TRPA1, present in some of the intradental nerves, which is implicated in the mediation of pain induced by cold 18,19 .   The results of this study revealed that the bleaching product containing oxalate showed little to no effect on the control and occurrence of dental sensitivity and did not exceed the performance of bleaching agents without desensitizers in any of the tests in this study, which demonstrably showed a lower performance than various products containing these agents 1 . Given this context, we emphasize the systematic review performed by Cunha-Cruz, et al. 7 (2011) that concluded that available evidence suggests that oxalates are not effective to decrease sensitivity.

Time / Products
The considerable occurrence of gingival tissue irritation in the hemi-arch treated with the bleaching agents that contained oxalate should also be emphasized. Consequently, we can infer that the presence of this salt may be a primary cause of the irritation. Another hypothesis to consider is the pH difference between the bleaching products used.
Although the two products had pH values close to neutral, the bleaching agent that contained oxalate was slightly more acidic. However, although there are reports of gingiva sensitivity during the bleaching treatment, there are no reports of the bleaching treatment causing severe harm to the gingiva 16 .
Nevertheless, some reports still report the efficiency of oxalate salts in controlling sensitivity when applied directly on the dental tissues 11,24 , stimulating new comparative studies, relating the work of different concentrations of oxalate with its cytotoxicity, collateral effects, and effectiveness 12,23 .

Conclusions
The results obtained in this study allow us to affirm that dental bleaching performed with carbamide peroxide with potassium oxalate in the composition did not modulate the occurrence and intensity of spontaneous sensitivity, nor reduced the dental sensitivity threshold when a thermal stimulus was used.