Comparing the effect of photobiostimulation, pressure and topical anesthetic gel on reducing pain during maxillary infiltration injection: a clinical trial study

Abstract

Background

Pain control during needle insertion reduces stress and increases collaboration between the patient and the dentist. The aim of this study was to compare the effect of photobiostimulation, pressure, and topical anesthetic gel on reducing pain during infiltration injection.

Materials & methods

A participant- and operator-blinded crossover clinical trial was conducted using 16 healthy volunteers ranging from 20 to 40 years of age. Each of the four interventions was done for each person at intervals of one week: (1) Photobiostimulation (photobiomodulation therapy, PBMT) using low-power diode laser with 808 nm, 400 mW continuous wave at an applied energy density of 2 J/cm². (2) 20% benzocaine topical anesthetic gel. (3) Pressure and (4) Control group. Then injection of 0.6 mL 2% lidocaine into the buccal mucosa of the maxillary canine was done. All subjects recorded pain using the visual analog scale (VAS). The Friedman and Dunn tests were used for data analysis.

Results

The mean scores of VAS for the laser, gel, pressure, and control groups were 1.43, 2.90, 1.78, and 3.15, respectively. The mean pain level in the laser group (p = 0.02) and pressure (p = 0.03) was lower than the control group.

Conclusion

Within the limitations of this small split-mouth trial, photobiomodulation therapy (PBMT) and local pressure appear to reduce pain during maxillary infiltration injection, whereas 20% benzocaine gel did not differ significantly from the control.

Trial registration

Iranian Registry of Clinical Trials, IRCT20141222020396N2; registered 21 January 2018.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-026-09153-1.

Introduction

One of the concerns of dentists is the anxiety control of patients during the local anesthetic injection. Over 25% of adults have been reported to be afraid of injections [1]. Syringe and needle phobia have been reported as a significant cause of anxiety among dental patients [2]. Various methods have been introduced to reduce pain during the injection of local anesthetic drugs [3], including anesthetic solutions, anesthetic patches, pressure on the injection site, buffering of the anesthetic solution, heating of the anesthetic solution, and a two-stage injection technique used to overcome the problem, which had different degrees of success [4–6].

Various factors such as needle diameter, anesthetic temperature, pH of the injection site, and the technique of injection affect pain perception during injection [7–9].

Today, numerous studies have shown that photobiostimulation using low-power lasers, hereafter photobiomodulation therapy (PBMT), in addition to their anti-inflammatory properties, are also useful in reducing neural activity [10, 11]. Recent studies have shown that photobiostimulation is effective in reducing pain perception in subcutaneous and intramuscular injections [12]. Some studies have suggested the efficacy of laser in the oral cavity as a method of anesthesia [13, 14]. However, evidence directly comparing PBMT with simple, low-cost alternatives such as local pressure and topical anesthetic gel during intraoral infiltration remains limited and inconsistent. Clarifying which of these readily available techniques most effectively reduces injection pain has direct clinical relevance for routine dental practice and for improving patient cooperation. Therefore, this study aimed to compare photobiostimulation by low-level diode laser irradiation, benzocaine gel and pressure on pain relief during infiltration injection of local anesthesia.

Materials and methods

According to the results of Nakamura et al. study using one-way ANOVA considering α = 0.05, β = 0.2 with a mean of 2.2 and the effect size equal to 0.93, the sample size of 16 was obtained [15]. Sampling was done randomly using a random number table. The priori sample size was estimated using one-way ANOVA, following the source study; because the VAS pain scores were ordinal and not normally distributed, the final analysis was performed with non-parametric tests (Friedman test with Dunn post-hoc).

This was a randomized, four-period crossover trial. Every participant received all four interventions, one per weekly session, in a randomized order generated from a random-number table, and the allocation order was concealed from the participants and from the operator who recorded the outcome. To support operator blinding, the laser handpiece was prepared and the laser activation—including aiming (“shooting”) of the beam and operation of the foot pedal—was carried out by a separate operator, so that the clinician who performed the injection and recorded the pain score remained unaware of whether the laser was actually emitting. The complete laser safety protocol (including protective eyewear for everyone present) was applied identically across all four groups, so that safety-related measures could not reveal which intervention was active. The one-week interval between sessions served as a washout period to limit carry-over effects (Fig. 1).

Fig. 1.

CONSORT flow diagram of the split-mouth crossover trial

All experimental procedures on patients who participated in this clinical trial were approved by the Local Ethical Committee of Tehran Azad University of Medical Sciences, in accordance with the Declaration of Helsinki, (IR.IAU.DENTAL.REC.1396.22). Moreover, the proposal of this study was reviewed, confirmed and recorded in the Iranian Clinical Trial Center (code No: IRCT 20141222020396N2).

Of 30 volunteers initially screened, 18 eligible non-smokers who signed the informed-consent form were enrolled. Two participants did not complete all four sessions and were excluded, leaving 16 participants (9 male and 7 female), aged 20–40 years and free of contributing systemic conditions, in the final analysis.

Inclusion criteria: healthy, non-smoking adults aged 20–40 years, with no contributing systemic disease and no ulcers or inflammation of the canine buccal mucosa, who signed the informed-consent form. Exclusion criteria: People with systemic diseases, history of trauma to the maxillofacial region, and the presence of ulcers or inflammation in the canine buccal mucosa. Volunteers who had taken analgesics, sedatives, or anti-anxiety medication within 72 h before injection, or who were unwilling to continue for any reason, were excluded from the study.

Each of the four interventions was done for each person at intervals of one week: (1) Photobiostimulation using low power diode laser with wavelength of 808 nm, power of 400 mW, tube with radius of 0.3 cm, diameter of 0.6 cm, surface area of 0.282 cm² with continuous wavelength and dose of 2 J/cm² for 12.5 s (Astar, Poland) (2). Benzocaine group: 20% benzocaine topical anesthetic gel (Prime Gel, Chicago, Illinois, USA) was applied to the injection site for 2 min before injection; the inactive laser tube head was then placed on the mucosa to mimic laser irradiation (sham) (3). Using the rubbing method, applying pressure for 2 min by laser tube head (without irradiation) to find the pale-colored (blanched) area of the mucosa (Sham) and (4) Control group, which had a passive laser tube without irradiation (Sham).

In each session, every volunteer received one of the four interventions according to the randomized order, so that all participants had received all four interventions by the end of the study. In all cases, the buccal mucosa of maxillary canine teeth was considered for injections. In order to make all groups uniform, the head of the laser tube was impregnated with ultrasound gel (PolyGel, Tehran, Iran) to match the sensation of gel contact with the mucosa.

The buccal mucosa in the upper canine area was dried with a cotton roll for 30 s. In the laser group, ultrasound gel was applied to the target area before laser irradiation. In the anesthetic gel group, the laser tube was coated with a barrier and merely pretended to be irradiated. In the pressure group, the laser tip was smeared with the ultrasonic gel and then pressured to the mucosa of the injection site for 2 min using the tube head. In the control group, the ultrasound-gel-coated laser tip was simply placed against the mucosa in non-irradiating mode, with no active intervention.

Then, the short 27-gauge needle (Ava dental needle, Tehran, Iran) was inserted deep in the buccal vestibule of the tooth, oblique to the apex of the tooth; after negative aspiration, 0.6 mL of 2% lidocaine with 1:80,000 epinephrine (Exir, Tehran, Iran) was gently injected over 20 s. The pain was measured immediately after the injection using the VAS system. Using this scale, each participant marked their pain level on a 10-cm horizontal line anchored by 0 (no pain) and 10 (most severe pain); the distance from zero was then measured with a graded ruler to obtain the score (Fig. 2). The Friedman and Dunn tests were used for data analysis. Kendall’s W was reported as an effect-size measure, and Hodges–Lehmann median differences with 95% confidence intervals were calculated for the comparisons with the control group. The statistical significance level was set at p < 0.05.

Fig. 2.

The 10-cm Visual Analog Scale (VAS) used to record injection pain

Results

This participant- and operator-blinded crossover controlled clinical trial was conducted on 16 volunteers ranging from 20 to 40 years who met the inclusion criteria. The sample comprised 9 (56.3%) male and 7 (43.7%) female patients.

Pain perception during injection was lower in the laser-treated group and pressure group than in the control group, and this difference was statistically significant (p = 0.02 and p = 0.03), but the benzocaine gel group showed no significant difference compared to the negative control group (p = 0.17). The mean pain score in the laser group was lower than the other experimental groups, but it was not significantly different. The mean pain perception in the laser vs. gel group (p = 0.08) and laser vs. pressure group (p = 1.00) was not significant. The mean pain score in the pressure group was lower than the gel group, but it was not statistically significant (p = 0.06). (Table 1)

Table 1.

Pain perception (VAS) during injection in the experimental and control groups

Intervention before injection	Mean ± SD	Median [IQR]	p value vs. control
PBMT (low-level laser, 808 nm)	1.43 ± 1.42	1.00 [0.00–2.25]	0.02
20% topical benzocaine gel	2.90 ± 1.52	3.00 [1.88–3.25]	0.17
Pressure at the injection site	1.78 ± 1.37	1.25 [1.00–3.00]	0.03
Negative control group	3.15 ± 1.70	3.00 [2.00–4.00]	—

Friedman test: χ² = 16.61, df = 3, p < 0.001; Kendall’s W = 0.35 (moderate effect)

p values are from Dunn post-hoc comparisons with the control group

The overall difference among the four conditions was significant (Friedman test, χ² = 16.61, df = 3, p < 0.001; Kendall’s W = 0.35, indicating a moderate effect). Median [interquartile range] VAS scores were 1.00 [0.00–2.25] for PBMT (laser), 1.25 [1.00–3.00] for pressure, 3.00 [1.88–3.25] for benzocaine gel, and 3.00 [2.00–4.00] for control. Compared with control, the median pain reduction was 1.50 (95% CI 0.50–2.50) for PBMT and 1.50 (95% CI 0.50–2.50) for pressure, whereas the difference for benzocaine gel was not significant (0.50, 95% CI − 0.50 to 1.25).

A formal comparison of pain scores between male and female participants was not performed. With only 9 men and 7 women, a sex-stratified subgroup analysis would have been substantially underpowered and prone to unstable or spurious estimates; such a comparison was also not pre-specified, and the design was powered for within-subject rather than between-sex contrasts. Sex-related differences in injection pain therefore remain to be examined in adequately powered future studies.

The recorded VAS scores in the PBMT (laser) and pressure groups ranged from 0 to 4, whereas the maximum scores reached 6 in the gel group and 8 in the control group (Fig. 3).

Fig. 3.

Distribution of VAS injection-pain scores by group (n = 16). Boxes show median and interquartile range; points are individual scores

Discussion

This study was carried out to investigate the techniques used to reduce pain during the injection of local anesthetic drugs. The results showed that PBMT (laser) pretreatment and pressure during injection were effective in reducing the pain of infiltration in the maxillary anterior region. This study was performed in the maxillary canine tooth because it is one of the most painful areas of intraoral injection [16].

According to the findings, the pain during injection was lower in the laser and pressure pretreatment group than in the control group. The mean pain score in the laser group was lower than the other groups, but it was not statistically significant compared to the gel and pressure groups. Recent high-level evidence, including a 2025 meta-analysis by Hakimiha et al., confirms that photobiomodulation (PBMT) also termed low-level laser therapy (PBMT) leads to a significant reduction in injection pain compared to control interventions, with consistent efficacy observed in both adult and pediatric populations [17]. A recent split-mouth, placebo-controlled randomized trial by Babaei-Zarch et al. (2025) similarly reported that photobiomodulation significantly reduced dental injection pain compared with a placebo, further supporting the analgesic efficacy of PBMT observed in our study [18].

F. Ghaderi et al. investigated the low-dose gallium-aluminum-arsenide laser to reduce pain during injection [16]. The mean pain of the control group in the present study (mean = 3.15) was higher than in their study (mean = 1.9). This difference was because the control group did not receive any intervention in this study, whereas they received benzocaine gel before injection into the maxillary canine teeth in their control group. They found no significant difference between the control group and the laser group, which contrasts with the numerically lower pain scores we observed in the laser group compared with the gel group; in our study, however, this laser-versus-gel difference did not reach statistical significance (p = 0.08). This pattern is consistent with a pain-reducing effect of PBMT that does not appear to depend on a topical anesthetic, although the present small crossover trial cannot establish this independence definitively.

Another study by Sattayut was a double-blind study comparing low-power laser, benzocaine anesthesia gel, and pressure [19]. That study found no significant difference among the groups, which is consistent with our overall finding; however, in line with our results, benzocaine gel was less effective than pressure or laser, and the laser parameters used differed from ours. The effectiveness of benzocaine gel in the Sattayut study can be explained by palatal injection instead of buccal injection, which involves a more superficial injection closer to the superficially anesthetized mucosa. Further supporting the variable efficacy of gel, a 2023 randomized controlled trial by Khan et al. in children found that photobiomodulation (PBM) was significantly more effective in reducing injection pain and anxiety compared to topical anesthesia, precooling, and vibration [20].

According to the result of the Lee study, the use of benzocaine gel is effective in alveolar mucosal anesthesia before injection, but not in the palatal area, because of the thicker and tighter mucosa, which encloses nerves in the area [21]. In the present study, the benzocaine group differed from the control group only in the presence of the gel, since both received the same sham laser-tube application; this isolates the pharmacological effect of benzocaine from any procedural or placebo effect. The lack of a significant difference between gel and control may also relate to application time: the gel was applied for 2 min, whereas some studies report greater efficacy with a longer pre-application (e.g., 5 min), which allows deeper mucosal penetration. The relatively short, fixed application time together with the thickness of the buccal mucosa may therefore have limited the anesthetic effect of benzocaine in our study. Beyond topical gels, PBMT has demonstrated efficacy in more challenging anesthetic scenarios. A 2024 randomized controlled trial by Mann et al. assessed PBMT’s effect on anesthesia depth during endodontic therapy for symptomatic irreversible pulpitis in mandibular molars. They reported that participants receiving PBMT had significantly lower pain scores and a reduced need for supplemental injections, indicating its value as an adjunct even for inferior alveolar nerve blocks [22]. Recent studies in pediatric populations reinforce the positive profile of PBMT. Research by Hamouda et al. (2024) and Uçar et al. (2023) concluded that laser photobiomodulation is a promising non-pharmacological technique that reduces injection pain without compromising anesthesia efficacy and is well-accepted by children [23, 24].

The difference between the control and pressure groups in our study can be explained based on the gate control theory, because superficial nerve stimulation prevents the transmission of neuronal potential in deep neurons [10, 25]. Pain is often transmitted through the C-type nerve fibers to the spinal cord and brain. These fibers are slower than the myelinated A-type nerve fibers, which are on the surface of the skin. The theory suggests that pain can be reduced by stimulating A-type nerve fibers that are faster than C-type pain fibers. In other words, arousing another sensation, such as pressure or contact, can block the pathway of the nerve message from pain.

The lowest mean pain score, as well as the minimum reported pain, was for the laser group, which can be explained by the Chow et al. study. This mechanism is due to a decrease in the potential rate of the nerve free-end membrane. Low-power laser reduces mitochondrial membrane potential and inhibits potential axonal transfer [10]. The low-power laser reduces C-fiber activity; moreover, bradykinin release also increases the pain threshold by enhancing endorphin synthesis. It may also have significant neuropharmacological effects on the synthesis, release, and metabolism of a set of neurochemicals such as serotonin and acetylcholine in the central nervous system and histamine and prostaglandin on peripheral nerves [26]. Beyond these direct neural effects, PBMT also modulates the local biological response to tissue stimulation; for example, low-level laser irradiation has been shown to influence inflammatory and bone-remodeling mediators such as osteoprotegerin and RANKL, supporting a broader anti-inflammatory and tissue-modulating role that may contribute to its analgesic action [27].

Numerous studies have reported improved pain control and tissue repair through low-level laser irradiation. Several studies pointed to the effect of laser compared to topical lidocaine in reducing the pain of needle entry in intramuscular injection; for this reason it works better than superficial anesthetic agents [12, 28]. Low-power lasers are effective in relieving pain and improving the condition in chronic articular problems by affecting a large number of immune cells such as fibroblasts, macrophages, and lymphocytes, as well as reducing inflammation [19].

The different results of laser application in different studies are due to different parameters in the application of this device, including different wavelengths, energy, exposure time, device power, type of target tissue, and physiological conditions. Due to the lack of a single protocol, different power and energy have been used in different studies for this purpose, making it difficult to compare [29–31]. This critical limitation is strongly echoed in recent literature. The 2025 meta-analysis by Hakimiha et al. reported notable heterogeneity (I² = 91.79%) among studies, primarily attributed to the wide variation in PBMT parameters [17]. Similarly, a 2024 systematic review by Altuhafy et al. concluded that further standardized studies are needed [32]. Importantly, a 2025 systematic review and meta-analysis by Shekarchi et al., while also concluding a statistically significant overall effect for PBMT, highlighted the persistent inconsistency in individual study outcomes, particularly in direct comparisons with topical anesthesia in children. This underscores that despite positive meta-analytic trends, the clinical translation of PBMT is highly sensitive to specific study protocols [33].

Another study by Nakamura et al. aimed at improving pain control during needle insertion by examining various topical anesthetics before injection in the canine tooth [15]. This is a comparative study between the use of benzocaine, lidocaine, and lidocaine with epinephrine and the control group 2 and 5 min before injection. The results also showed a decrease in pain reporting with the use of benzocaine, which was pronounced 5 min before injection. However, in the end, there was no statistically significant difference with the control group. Notably, a recent randomized controlled split-mouth trial by Ayaz et al. (2025) also found no significant difference in pain scores between an PBMT-treated side (635 nm, 10 J/cm²) and a control side in adults undergoing endodontic procedures. This study is crucial as it demonstrates that not all laser protocols yield a positive effect, directly supporting the argument that the optimization of parameters—such as wavelength, energy density, and irradiation time—is not merely an academic point but a fundamental clinical determinant of efficacy [34].

A study by Milani et al. compared the effect of topical anesthesia with EMLA (lidocaine-prilocaine cream), topical benzocaine and pressure on pain during infiltration in the maxillary canine [35]. The EMLA cream showed significantly reduced pain compared to the control group and also proved to be much more useful than benzocaine in reducing pain during injection. Nevertheless, there was no significant difference in pain relief compared to the pressure group.

Freitas et al. conducted a study to investigate the local anesthesia of 20% benzocaine in pain relief during injection of the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN) [36]. The results showed that benzocaine and placebo had a similar effect on perception of pain during both types of injection, which is in line with the results of the present study.

Strengths and limitations. This study has several strengths: it used a participant- and operator-blinded, crossover design, and all injections were performed by a single operator, which minimized inter-operator variability. The crossover design reduced inter-individual variability and controlled for many confounding variables.

The present study, despite its participant- and operator-blinded design, has several limitations. The use of convenience sampling and a relatively modest sample size limits the statistical power and may affect the generalizability of the findings. A fundamental constraint is the application of a single, fixed set of PBMT parameters. This reflects a broader, well-documented challenge in photobiomodulation research, where the absence of standardized protocols for wavelength, power, irradiation time, and energy density creates significant heterogeneity across studies and hinders direct comparison of results. This issue is quantitatively underscored by a recent meta-analysis on dental injection pain, which reported notable heterogeneity (I² = 91.79%) primarily attributable to variations in laser parameters [17], and qualitatively supported by other reviews calling for more standardized research [32]. The null findings from studies using different parameters, such as the 635 nm protocol by Ayaz et al. (2025), serve as a concrete example of how clinical efficacy is critically dependent on optimal dosing [34]. In addition, although the order of interventions was randomized and a one-week washout was applied, the pain and anxiety experienced during the first session may have influenced pain perception in subsequent sessions, and a potential order or carry-over effect cannot be fully excluded. The success of participant and operator blinding was not formally assessed. Moreover, the distinct sensory characteristics of the four interventions (pressure application, benzocaine gel, sham laser, and active PBMT) may have made complete participant blinding difficult to achieve, so the study is more accurately described as participant- and operator-blinded rather than fully double-blind. The pressure intervention was applied manually by a single trained operator to a standardized clinical endpoint (firm, constant pressure maintained for 2 min until transient blanching of the mucosa), but the actual force was not instrumented or quantified, which limits its reproducibility. Finally, the reliance on subjective self-reporting for pain assessment, although using validated scales, remains inherently susceptible to unquantifiable psychological influences.

Conclusion

Within the limitations of this small split-mouth trial, photobiomodulation therapy (PBMT) with an 808-nm low-power laser and local pressure significantly reduced pain during infiltration injection in the anterior maxilla, whereas 20% benzocaine gel did not. These findings should be interpreted cautiously given the modest sample size and the use of a single, fixed set of laser parameters. Standardization of PBMT parameters (wavelength, power, energy density, and irradiation time) and larger, adequately powered trials are needed before firm clinical recommendations can be made.

Authors’ contributions

M.V. : Conceptualization, Formal analysis, Writing – review & editing. Z.H. : Investigation, Methodology.STS: Software, Supervision, Validation, Writing – original draft. MR: Writing – review & editing (manuscript editing, revision, and proofreading), and corresponding author.

Funding

None.

Data availability

The datasets of the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by the Local Ethics Committee of Tehran Azad University of Medical Sciences (IR.IAU.DENTAL.REC.1396.22), in accordance with the Declaration of Helsinki, and was registered with the Iranian Registry of Clinical Trials (IRCT20141222020396N2). All participants provided written informed consent before enrolment.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.