Dentin hypersensitivity (DH) is a common dental complaint that patients experience when eating, drinking, or brushing their teeth, negatively affecting their quality of life.^[1] This sharp, short-term pain is caused by palpable, thermal, chemical, or osmotic stimuli, and there is no dental impairment.^[2] DH is found in both sexes and is more common in adults. Usually, the facial surface of the tooth in the cervical region is involved. Periodontal treatments directly increase DH by exposing the dentinal tubules of the root.^[3]

Hypersensitivity is mainly related to dentin exposure. Dentinal tubules are normally protected by enamel on the crown or gingiva on the tooth’s root surface. When the enamel is removed or the gingiva recesses, the tooth would be susceptible to stimuli. The most accepted theory about this sensitivity is the “hydrodynamic theory” proposed by Branstrom in 1964.^[4,5] According to it, when the dentin surface is exposed to stimuli, fluid flow in dentin tubules increases; therefore, it changes the pressure and stimulates pressure-sensitive nerve receptors in dentin.^[6] DH has various degrees of pain; however, it can alter patients’ daily activities and lead them to the dentist. The basic principle for treatment is to change the fluid flow in the dentinal tubules by blocking or narrowing them.^[4] Many treatment methods are now available, such as using adhesives, varnishes, dental bonding materials, periodontal grafts, and restorative procedures with different results. The most common is home remedies.^[7] At present, toothpaste containing fluoride seems to have primary and secondary preventive effects against dentinal hypersensitivity, but therapeutic benefits can be increased by adding some ingredients.^[8] Chemical compounds available for this purpose are potassium or ferrous oxalates, potassium nitrate, stannous fluoride, sodium fluoride, sodium monofluorophosphate, and strontium chloride.^[9]

Propolis is a yellow resin compound of beehives that contains 300 components.^[10] It is mainly composed of resin (50%), wax (30%), essential oils (10%), pollen (5%), and other organic compounds (5%).^[11] Propolis blocks the fluid flow by sealing the tubules. It is a source of chemicals, especially active flavonoids. Flavonoids have tissue regenerative activity and are the main stimulants of dentin formation.^[9,12] During reactions with dentin, these bioflavonoids form crystals in dentin tubules, thereby reducing fluid flow.^[13] Propolis content varies according to its botanical origin and geographical location.^[14]

Casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) is a milk nano complex. Casein phosphopeptide allows high concentrations of calcium, phosphate, and fluoride ions to be stabilized in a semi-stable solution that can be used to enhance remineralization. The calcium and phosphate ions released from CPP-ACPF are diffused through the enamel pores and deposited in the enamel crystals. Human studies have successfully shown the CPP-ACPF potential to prevent enamel demineralization and increase the remineralization of enamel defects.^[15] Mineral deposition inside dentin tubules increases and blocks the dentinal tubules; therefore, the permeability and diameter of dentinal tubules are decreased by 85% or more, decreasing dentinal hypersensitivity.^[16]

Due to the high prevalence of DH in the community, which negatively impacts the quality of life,^[17] this study was conducted to compare the effectiveness of two kinds of desensitizing agents: GC^® MI-Paste Plus, which contains CPP-ACPF, and Herbex^® herbal toothpaste, which contains propolis. The ease of application, availability, and nature of these pastes, as well as contradictory reports in previous studies, encouraged us to do this study. The null hypothesis in this study is that there is no difference between the treatment groups in different times in the reduction of DH.

A total of 20 patients participated in the 8-week clinical trial, with 10 patients randomized to the Herbex^® herbal group (containing propolis) and 10 patients to the GC^® MI-Paste Plus group. Baseline demographic characteristics, including age and gender, were statistically similar between the two groups (P > 0.05) [Table 1].

As shown in Table 2, the interaction effect of time by group on VAS score was statistically significant. This finding implies that the improvement in VAS score in the two groups was different and the Herbex^® group showed a sharper decline in the mean of cold sensitivity score over time compared to the GC^® MI-Paste Plus group [Figure 2]. Both groups exhibited considerable improvements in mean VAS score of cold sensitivity during the follow-up period (P value for Time < 0.001) [Table 2].

While the mean VAS score for tooth sensitivity to cold was consistently lower in the Herbex^® group compared to the GC^® MI-Paste Plus group at all-time points after treatment, a statistically significant difference was only observed at 8 weeks after treatment (2.35 ± 0.408 vs. 3.95 ± 0.507; P = 0.014) [Figure 2].

The interaction effect of time by group on VAS score of tooth sensitivity to air was not statistically significant (P > 0.05) [Table 2]. Tooth air sensitivity score was significantly improved in both groups 8 weeks after treatment (P < 0.001) [Table 2]. However, this decline decelerated over time (polynomial coefficient [se] for time: 0.007 [0.001]; P < 0.001), indicating approximately a nonlinear sensitivity to air trend. There was no considerable difference between two groups in the mean VAS score of air sensitivity at any time point (P > 0.05) [Figure 3].

This study showed that using both GC^® MI-Paste plus containing CPP-ACPF and Herbex^® herbal toothpaste containing propolis reduced symptoms and pain intensity up to 8 weeks after starting treatment. Furthermore, Herbex^® herbal toothpaste was significantly more effective in the reduction of pain intensity in the 8^th week. Based on the comparison of the results of the cold test, the immediate response (15 min after the intervention) was not significantly different between the two groups, but the delayed response (2 months after the intervention) showed a significant decrease in the Herbal Toothpaste group. Furthermore, there was no significant difference in any of the immediate and delayed responses between the two groups in the airblast test. However, in each group, an immediate and delayed effect was observed in reducing tooth sensitivity pain. The average intensity of tooth sensitivity in all periods in both groups and by both tests was significantly lower than before treatment.

Tactile, cold, and evaporative stimuli have been recommended as reliable tests to measure DH, and it is recommended to use at least two hydrodynamic stimuli. The interval between tests should be long enough to minimize interaction between the stimuli. In the present study, the air blast test and the cold test were performed to measure DH. The air blast test was performed 5 min before the cold test to minimize interaction between stimuli.^[19]

Madhavan et al.^[21] compared CPP-ACPF, sodium fluoride, propolis, and placebo in treating DH. All three study groups showed a decrease in dentin sensitivity over 3 months compared to the control group. The propolis group showed the lowest mean of DH. The delayed response was seen in all three groups, especially in the propolis group. However, in the present study, only two groups were compared, and the results showed that the herbal toothpaste containing propolis was more effective than the toothpaste containing CPP-ACPF only in the 8^th week. Still, in Madhavan’s study in all periods (7, 15, 28, and 60 days), the propolis was more effective than CPP-ACPF.^[21] However, that study did not indicate the consistency and application method of propolis in the form of gel or toothpaste. On the other hand, Torwane et al. compared the 30% ethanolic extract of Indian propolis with Recaldent™ as positive control group containing CPP-ACP and sterile distilled water as negative control. In the airblast test, all three groups showed a significant reduction in dentin sensitivity, but unlike our study, CPP-ACP was significantly more effective and acted faster than propolis.^[16] It seems that fluoride in the CPP-ACPF-containing toothpaste (900 ppm) can react with ACP in the casein complex, causing the deposition of calcium fluoride and neutralizing both mineral components of this paste.^[22] This hypothesis may be considered the etiology for the lower effect of this paste in the 8^th week in the present study.

Mahesuti et al. compared a paste containing CPP-ACPF and a gel containing potassium nitrate to treat dentinal hypersensitivity. Both significantly reduced dentinal hypersensitivity, but there was no difference between these agents. Although potassium nitrate acted faster than MI Paste, but MI Paste had a longer performance after treatment than potassium nitrate.^[23] In the present study, the immediate effect of CPP-ACPF was determined in addition to the delayed effect which is consistent with the above study. MI Paste^® Plus contains glycerol which is a humectant that keeps moisture on the tooth’s surface by absorbing water. It seems that glycerol plug formation can be the primary mechanism of prevention of dental hypersensitivity in bleaching treatments. This was confirmed by the immediate effect observed in the present study. This process is later completed by calcium and phosphate ions sedimentation that maintains its effects for longer.^[24] Purra et al. compared saturated ethanolic propolis solution, 5% potassium nitrate, and distilled water. The results showed no significant difference between propolis and potassium nitrate in immediate, 1-month, and 3-month responses, and propolis was more effective than potassium nitrate only in 1- and 2-week assessments. According to this study, propolis is as effective as potassium nitrate in the immediate and delayed response.^[9]

Davari et al. showed that using Nd: YAG laser and propolis over three sessions progressively reduced the pain due to dentinal sensitivity. Pain reduction in each treatment session, relative to the previous session, was significant. Propolis was as effective as the Nd: YAG laser, which is the standard method for treating DH.^[25] The authors attributed this property of propolis to its high content of flavonoids, which block the tubules. Flavonoids can neutralize free radicals by binding to heavy metal ions, known as accelerators of radical production reactions. The propolis used in the mentioned study was a layer of 40% propolis gel with an overall 8000 ppm polyphenol content. It was applied to the tooth surface by microbrushes in three sessions. Nevertheless, in Davari’s study, noncommercial propolis gel and, consequently, different thicknesses were used on the teeth. In our previous study, propolis gel prepared by Green Plants Company positively but insignificantly reduced postinflammation after periodontal surgeries. However, the low viscosity was a limitation of this gel.^[26] One of the strengths of the present study is the use of commercially available toothpaste containing propolis, which facilitated its easier and constant use by all people.

Demydova’s study compared the effects of the diode laser, propolis ethanolic extract, fluoride varnish, and a combination of the laser and propolis treatments. The results showed that all agents were similar in the immediate effect. Furthermore, all four groups showed a significant decrease in the mean severity of dentinal sensitivity over 6 months. These findings on the immediate and delayed effects of propolis are in line with the present study.^[27]

Although our study demonstrated the individual effects of each paste in relieving dentin sensitivity compared to the baseline, it is recommended to explore these agents with sodium fluoride varnish as a positive control in future clinical studies. In our previous research,^[28] which was done on the percentage of open, semi-closed, and closed dentinal tubules, it was shown that the effect of Herbex^® herbal toothpaste containing propolis was more than sodium fluoride varnish in reducing the percentage of open dentinal tubules.

This study encountered numerous limitations as a result of the COVID-19 pandemic and associated issues, which made it impossible to conduct additional follow-ups and assess treatment outcomes over the long term. According to the above limitation and the difficulties in clinical trials such as patients’ cooperation, it seems that both Herbex^® herbal toothpaste containing propolis and GC^® MI-Paste Plus were effective in reducing DH after 2 months. Moreover, on one hand, GC^® MI-Paste Plus has a higher cost for patients, and on the other hand, Herbex^® herbal toothpaste is easier to use, more beneficial, and more cost-effective. Therefore, it seems that Herbex^® herbal toothpaste can be used as an alternative to MI paste to treat DH. However, more studies are needed to be more conclusive.

Both herbal toothpaste containing propolis and CPP-ACPF-containing paste for 2 months effectively reduced DH. However, after 2 months Herbex^® herbal toothpaste seemed to be more beneficial.