Blocking tubules technologies for dentin hypersensitivity in periodontal patients – pilot study

Periodontal patients often report dentin hypersensitivity (DH) caused by root surface exposure or periodontal treatment. Tubular blocking technologies in toothpastes are effective for pain relief, but no specific chemical/physical agent has been reported for periodontal patients. This double-blind randomized clinical trial compared the effects of three technologies in reducing DH in periodontal patients. Eighteen (18) participants were randomly assigned into three groups: SEN (NOVAMIN technology); REG (REFIX technology); REGK (REFIX technology + potassium citrate). Periodontal patients presenting with DH were evaluated at 6 moments: T1 and T2 immediately before and after scaling and root planing procedures (SRP); T3 after polishing sensitive areas with their assigned dentifrice and T4, T5, T6 after 2, 4 and 8 weeks of SRP respectively. Sensitivity was assessed by air blast (Schiff scale) and patients’ perceptions using the visual analogue scale (VAS). Data were analyzed by two-way repeated measures ANOVA complemented by the Tukey test with significance set at 5% (p <0.05). Preliminary outcomes revealed SEN, REG and REGP reduced DH in periodontal patients (n=18). All patients initially presented moderate to severe pain (64.3) and after treatment they reported mild pain (21.3). Similarly, the dentist evaluation showed significant reduction in DH with the use of the three technologies (2.26 to 0.56). No statistically significant differences were found between the three study groups for patients (p=0.751) and dentist evaluations (p=0.632). According to these preliminary outcomes, all three technologies equally reduced DH in periodontal patients. Clinical trials #NCT04422184

Various dental procedures, including periodontal therapy could result in the occurrence of DH. Scaling and root planing with partial or total removal of cementum and/or root exposure as a consequence of periodontal disease progression could be linked to DH (Van Loveren, 2013).
Currently, two methods for DH treatment are described in the literature: interruption of the response to pain stimulus which decreases nerves excitability or through obliteration of the exposed dentinal tubules (Van Loveren, 2013;Hu et al., 2018;Vilhena et al., 2020;Martins et al., 2020).
DH treatment presenting less invasive and more conservative forms should be considered in the decision making process for product recommendations (Canadian Advisory Board on Dentin Hypersensitivity, 2003). With that in mind, dentifrices are viable options since they introduce components that act as desensitizers in an effective, inexpensive and easily accessible way Among DH treatment compounds that are incorporated in dentifrices, potassium salts have been shown to be very effective (West, Seong & Davies, 2015;Martins et al., 2020). They have a depolarizing action on nerve fibers, reducing their excitability to the stimuli. Other important desensitizing compounds that act on the obliteration of dentinal tubules are: oxalates, Arginine, Hydroxyapatite, Bioglass and Silicon-based technologies (Patil, Naik & Suma, 2015;West, Seong & Davies, 2015;Amaechi et al., 2018;Van Loveren, 2013;Hu et al.,2018;Vilhena et al., 2020, Martins et al.,2020Canadian Advisory Board on Dentin Hypersensitivity, 2003;Boneta et al., 2013;Hu et al., 2013, Amaechi & Van Loveren, 2013Burwell, Litkowski & Greenspan, 2009). NOVAMIN® technology is extensively studied and indicated for HD, due to its obliterating property of dentinal tubules. The components in the mentioned technology are calcium and sodium phosphosilicate, which promote continuous remineralization (Lippert, 2013;Addy & Dowell, 1983).
Thus, this preliminary study compared the effect of three different technologies, NOVAMIN, REFIX and REFIX technology plus potassium citrate, in order to reduce DH in periodontal patients.

Methodology
This double-blind randomized clinical trial was approved by the Ethics Committee in Human Research (Protocol #3.325.186) and was conducted at the Periodontics Clinics of the Bauru School of Dentistry -University of São Paulo (FOB/USP). The study was registered on Clinicaltrials.gov (protocol #NCT04422184). The inclusion criteria were: patients diagnosed with periodontitis, ranging from 18 to 70 years old, healthy, without any allergy to the dentifrices components; patients who needed scaling and root planing procedures and who had at least 2 teeth with DH (incisors, canines or premolars). The exclusion criteria were: patients who were pregnant, in orthodontic treatment, who had oral tumors, caries, fractured teeth, suspected endodontic involvement or excessive mobility; patients who used medication that could mask the painful sensation or who had used desensitizing agents in the last 3 months.
After initial evaluation, patients received detailed information about possible causes of tooth root sensitivity. All selected patients received the dentifrices in packages with soft brush and dental floss. Experimental groups were divided in: • SEN (Sensodyne Repair and Protect powered by NOVAMIN)-positive control group • REG (Dentalclean Daily Regenerator powered by REFIX) • REGK (Dentalclean Daily Regenerator powered by REFIX + potassium citrate).
Patients received verbal instructions for brushing, which should be performed twice a day (morning and evening) during one minute. All brushings were performed exclusively with the dentifrices determined for each experimental group. DH parameters were evaluated by one trained and calibrated examiner using a scale described by Schiff et al (1994). The sensitivity to air blast (triple syringe) was evaluated during one second at a distance of one centimeter from the tooth surface that presented the sensitivity. Adjacent teeth were prevented from receiving the air blast by placing the examiner's fingers on them. Air blast sensitivity evaluation presented with scores ranging from: 0 = Tooth/Subject does not show sensitivity in response to air stimulation; 1 = Tooth/Subject responds to air stimulus, but does not request discontinuation of stimulus; 2 = Tooth/Subject responds to air stimulus, and requests discontinuation or moves from stimulus; 3 = Tooth/Subject responds to stimulus, considers stimulus to be painful, and requests discontinuation of the stimulus. Patient's perception of DH was also evaluated with a visual analogue scale (VAS), ranging from 0 being without any painful sensation to 100 being the most painful scenario. For the correct filling out of this scale by the patients, the examiner first instructed all in the same way. Immediately after the air blast, the examiner gave the scale for the patient to mark their sensitivity. Both professional and patient's parameters were evaluated at: T1 -immediately before scaling and root planing (SRP); T2 -immediately after SRP; T3 -after polishing sensitive areas with rubber cups and the dentifrice determined for each specific group of patients and T4, T5, T6 -after 2, 4 and 8 weeks of SRP Research, Society andDevelopment, v. 10, n. 13, e35101320398, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i13.20398 4 respectively. Patients were instructed to perform standard brushing exclusively with the dentifrice assigned to their group. These methodologies were based on the work of Docimo et al., (2009) and Hughes et al., (2010).
Mean values obtained from the evaluated teeth of each patient (professional and patient analysis) were calculated for the different periods (T1 to T6). The primary clinical outcome was the operator's assessment of sensitivity (Schiff scale). The secondary clinical outcome was patient-reported sensitivity. Data were analyzed by two-way repeated measures ANOVA complemented by Tukey test with the significance level set at 5% (p <0.05).

Results and Discussion
Preliminary outcomes demonstrated no statistical differences between groups for reduction in DH in the 18 periodontal patients (Figure 1), considering both evaluations done by the professional (p=0.632) and the patient (p=0.751).  According to the VAS data, SEN and REG presented significant reductions in sensitivity on T4, T5 and T6 compared to T1 (p<0.05). REGK presented a statistically significant reduction (p<0.05) on T6 compared to T1 (Figure 3). Research, Society and Development, v. 10, n. 13, e35101320398, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i13.20398 Periodontal procedures are frequently associated with DH due to exposure of dentinal tubules after SRP or the presence of gingival recession associated with periodontal disease progression (Van Loveren, 2013;Vilhena et al., 2020). According to preliminary results of this study, all three dentifrices tested reduced the DH during periodontal treatment and maintenance. These outcomes are in accordance with the literature, which describes the significant decrease in DH when treated with specific dentifrices in daily brushing (Patil, Naik & Suma, 2015;West, Seong & Davies, 2015;Amaechi et al., 2018;Van Loveren, 2013;Hu et al., 2018;Vilhena et al., 2020;Boneta et al., 2013;Hu et al., 2013). One of the tested dentifrices contains the extensively documented NOVAMIN technology and was considered the positive control group. The active ingredient of this technology is calcium sodium phosphosilicate ('bioglass'), capable of promoting the obliteration of dentinal tubules. NOVAMIN could be considered a gold standard technology, since the mechanism of action is based on the release of Na, Ca and P ions in the oral environment. These elements when incorporated into the dentin structure, have been shown to promote the formation of a layer of hydroxyapatite similar to enamel (West, Seong & Davies, 2015;Amaechi et al., 2018;Hu et al., 2018;Martins et al., 2020;Amaechi & Van Loveren, 2013;Burwell, Litkowski & Greenspan, 2009;Lippert, 2013;Shen et al., 2018;Hench & Jones, 2015;Philip, 2019).
Through research progression, the development of new technologies showing satisfactory results can improve the quality of life for these patients with DH6. The new technology used in this study was REFIX, an innovation in dental regeneration. REFIX Dental Technology is an Acidified Bioactive Complex designed by an association of organic compounds and ingredients containing Silicon, Fluoride and Phosphates. During brushing, this innovative formula binds into the tooth, catching scattered particles in the oral environment, mainly calcium and this complex forms a protective hybrid layer containing Silicon-enriched Hydroxyapatite. This layer, a protective shield similar to the original enamel is able to re-mineralize the surface and subsurface of the dental enamel and protect against acid attacks. When the dentin is exposed, this shield forms over and within the dentin tubules in order to relieve the pain caused by tooth sensitivity (Vilhena et al., 2020;Tomaz et al., 2023). One of the experimental groups in this study, included REFIX technology with the incorporation of potassium salt (REGK), however the reduction of DH was similar to the other two groups. Effective results for this new product have been shown in other previous studies (Hu et al., 2018;Canadian Advisory Board on Dentin Hypersensitivity, 2003). In this study however, the K salt presented no improvement in the performance of REFIX technology. This is probably related to the prompt tubule obliteration action provided by REFIX technology (Vilhena et al., 2020). Thus, the purpose of K salt in depolarizing nerve fibers did not improve the main action of dentinal tubules obliteration. However, these preliminary results could not define the possible benefit of incorporating K salt.

Conclusion
One limitation of this pilot study is the sample size, but it is important to observe that the three tested technologies presented the ability to decrease DH in periodontal patients. Another limitation was the lack of a negative control for comparative evaluation but for ethical reasons, this group (placebo) was not included. Despite that, our methodology used NOVAMIN technology as a positive control for this comparison.
According to these preliminary outcomes, the three different technologies reduced DH equally in periodontal patients.
Further investigation with a larger sample size is necessary to confirm these outcomes.