Pain management in acute apical abscesses with valacyclovir monotherapy after emergency chamber opening: a prospective randomized clinical study

1. Introduction

An abscess typically involves the accumulation of pus within a cavity due to tissue liquefaction [1, 2]. Dental abscess, dentoalveolar abscess, and odontogenic abscess are terms frequently interchanged to describe abscesses that develop in the tissues surrounding the tooth. These abscesses may originate from an endodontic infection, referred to as acute apical abscess, or a periodontal infection, such as periodontal abscess or pericoronitis [3]. Among dental abscesses, acute apical abscess is the most common type [4].

Acute apical abscesses are a common dental emergency characterized by severe pain, swelling and localized inflammation around the apex of a tooth’s root [5]. These abscesses typically arise from bacterial infection of the dental pulp, often caused by untreated dental caries or dental trauma. Despite advances in dental care, acute apical abscesses remain a significant source of pain and discomfort for patients, necessitating prompt and effective management strategies [6]. Acute apical abscesses are triggered by inflammation within the endodontic system, typically exacerbated by mixed bacterial infection, with anaerobic species being the most predominant. While the pathogenesis of these abscesses is primarily attributed to bacterial mechanisms, emerging evidence suggests a potential role of Herpes-virus infection in the development of apical periodontitis [7].

In certain cases of symptomatic apical periodontitis, the underlying etiology shares similarities with that of marginal periodontitis. Aggressive forms of periapical pathosis may develop due to interactions among herpesviruses, bacteria, and host immune responses, mirroring the processes observed in marginal periodontitis [8, 9]. In endodontic disease, herpesviruses are believed to enhance the virulence of bacterial pathogens by facilitating their attachment to and invasion of epithelial cells. Antibiotics, such as Amoxicillin and Penicillin V, are commonly prescribed to manage acute apical abscesses, with Clindamycin being an alternative for patients allergic to Penicillin V. However, it is essential to use antibiotics judiciously and reserve them for cases with worsening symptoms. Treatment should be stopped once symptoms improve [10, 11, 12]. According to clinical guidelines, pulpectomy or pulpotomy is recommended as the primary emergency treatment for acute apical abscesses [13].

Evidence suggests that antibiotics are ineffective when adequate debridement and drainage are performed in cases of apical abscess, pulp necrosis or localized endodontic infection, as demonstrated in randomized clinical trials [9]. Herpes viruses, particularly Herpes simplex virus (HSV), have been linked to the exacerbation of dental infections and levated postoperative pain following dental procedures [14]. Valacyclovir, an antiviral medication, works by inhibiting HSV replication and has been effectively used in managing herpetic infections across various medical contexts [15].

Given the potential role of HSV in dental infections and associated pain, there is an emerging interest in exploring the utility of valacyclovir as an adjunctive therapy in the management of acute apical abscesses [16]. Conventionally, the primary approach to managing acute apical abscesses involves emergency chamber opening, aimed at relieving pain by draining the abscess and facilitating the removal of infected tissue [17]. Although several studies have investigated the use of antiviral agents along standard dental treatments, a gap remains in the literature regarding the efficacy of valacyclovir monotherapy in pain management following emergency chamber opening for acute apical abscesses.

Therefore, this randomized clinical trial aimed to evaluate the effectiveness of valacyclovir as a standalone therapy in alleviating postoperative pain and reducing the risk of recurrent infection in patients presenting with acute apical abscesses.

2. Materials and methods

This randomized controlled clinical trial was conducted at the Department of Operative Dentistry and Endodontics, Dr. Ishrat-Ul-Ebad Khan Institute of Oral Health Science, Dow University of Health Sciences, after obtaining an ethical approval (IRB-2517/DUHS/Approval/2022/890) from October 2022 to May 2023. The clinical trial was also registered on Clinical-Trials.gov ID: NCT06344195. This study included patients aged 18 years or older presenting with moderate to severe pain due to pulp necrosis and acute apical abscess. Exclusion criteria included patients currently taking antibiotics or antivirals, smokers, individuals with unusual tooth anatomy or inaccurate diagnosis, pregnant or nursing mothers and those allergic to valacyclovir.

Sample size calculation was performed using PASS software version 11 (NCSS, LLC, Kaysville, UT, USA). Based on previous research [18], which indicated the absence of pain in both the treatment and placebo groups, a total of 82 patients (41 per group) were recruited for the study over a period of 8 months. Eighty-two patients who met the inclusion criteria and provided consent to participate in the study underwent emergency chamber opening and pulpectomy. Pulpectomy was performed in both case and control groups using manual K-files upto file#25 after determining the working length with apex-locator. Sodium Hypchlorite (5.25%) solution was used as irrigant during the procedure. Upon completion, the root canal was dried using paper points and filled with intracanal medication (Calcium Hydroxide (metapex)). Cotton was placed at the orifice, and the chamber was sealed with temporary filling material (3M^TM cavit^TM-G). Patients were then discharged with prescribed medication free of cost (Fig. 1). Prior to discharge and prescription, patients were randomly divided into two groups. Group A (case) received a prescription of valacyclovir (2 g immediate dose followed by 500 mg 2 times daily for 3 days) along with the analgesic Naproxen sodium 550 mg (to be taken as needed, SOS). Group B (control) was prescribed only Naproxen Sodium 550 mg (SOS). The principal investigator contacted the study participants daily at a preset time over 6 days to evaluate their pain levels using the numeric rating scale (NRS) and to document the analgesic usage. After two weeks, all participants underwent conventional root canal treatment as part of the study protocol. The schematic flow of patients throughout the study is illustrated in the Fig. 2.

Fig. 1.Patient with acute apical abscess underwent an emergency chamber opening.

Fig. 2.The schematic flow of patients throughout the study.

SPSS 20 (IBM, Chicago, IL, USA) was used to analyze the data. Continuous variables were represented as mean standard deviation, while categorical variables were represented as frequency and percentage. Normal distribution was verified using the Shapiro-Wilk test. The Chi square test was employed to compare the results, with a p-value of 0.05 considered statistically significant.

3. Results

The demographic characteristics of the studied participants are summarized in Table 1. The mean age of participants in the Case group was 33.17 years with a standard deviation of 8.84, while in the Control group, the mean age was 32.12 years with a standard deviation of 7.93.

The results show variations in pain scores between Group A and Group B on different days throughout the study period (Table 2).

Day 1 Pain Scores: The mean pain score on Day 1 was higher in the Case Group compared to the Control Group, although the difference was not statistically significant.

Day 2 Pain Scores: On Day 2, the mean pain score was higher in the Case Group compared to the Control Group, but the difference was not statistically significant.

Day 3 Pain Scores: The mean pain score on Day 3 was higher in the Case Group compared to the Control Group, but the difference was not statistically significant.

Day 4 Pain Scores: On Day 4, the mean pain score was significantly higher in the Case Group compared to the Control Group.

Day 5 Pain Scores: The mean pain score on Day 5 was higher in the Case Group compared to the Control Group, although the difference was not statistically significant.

Day 6 Pain Scores: On Day 6, the mean pain score in the Case Group was slightly higher than in the Control Group, but the difference was not statistically significant.

4. Discussion

The development of acute apical abscess, a severe endodontic condition, arises from opportunistic bacterial infection, potentially coupled with latent herpesvirus coinfection [19]. This symbiotic relationship between herpesviruses and bacteria initiates a detrimental cycle, where bacterial virulence factors in the pulp and periodontal tissues may activate herpesviruses. Consequently, herpesvirus reactivation impairs the local immune defenses, enabling resident bacteria to proliferate in peripheral tissues, thereby exacerbating the condition [20, 21]. While herpesviruses and viral particles are detected, they are not considered indispensable for the development of acute abscesses and cellulitis originating from endodontic sources [22].

In our study, valacyclovir monotherapy did not show a significant difference in pain scores between the Case and Control groups over the six-day assessment period. This suggests that valacyclovir monotherapy alone may not provide substantial pain relief compared to standard treatment alone. However, in a study by Sabeti et al. [18], which investigated the combination of valacyclovir with amoxicillin, a significant improvement in pain management was observed in patients with acute apical abscesses. Patients receiving the combined therapy experienced reduced pain levels and lower analgesic usage throughout the study duration, suggesting the potential of valacyclovir as an adjunctive treatment for pain relief in such cases [18].

The differing outcomes between our study and Sabeti et al.’s [18] research may be due to differences in treatment protocols, patient populations or study methodologies. Our study focused solely on valacyclovir monotherapy, while a study by Sabeti et al. [18] evaluated the combination of valacyclovir with amoxicillin. The synergistic effect of valacyclovir and amoxicillin could have contributed to the superior pain management observed in their findings. Additionally, differences in patient demographics, disease severity, or follow-up protocols could have affected the outcomes of the two studies.

Moreover, Bandara et al. [23] proposed that the elevated detection of herpes virus in certain studies could be influenced by the surgical procedure and potential contamination from the marginal area. Li et al. [19], on the other hand, revealed that irreversible pulpitis and apical periodontitis exhibit notably higher levels of Epstein-Barr virus (EBV) compared to HSV-1. Their findings imply that the herpes virus is less likely to be associated with these endodontic conditions, suggesting minimal involvement of the herpes virus in the development of endodontic conditions.

Herpes virus chemotherapeutics are effective against viruses during the lytic phase but are believed to be ineffective during the latent phase, thereby limiting the application of valacyclovir to disease-active periodontitis [24]. Valacyclovir’s lack of efficacy against bacteria limits its ability to treat acute apical abscesses, which are predominantly bacterial infections. Valacyclovir is an antiviral medication that targets viruses, particularly herpesviruses and inhibits their replication. However, it lacks antibacterial properties, rendering it inadequate for directly addressing bacterial infections commonly associated with acute apical abscesses [25].

In management of acute apical abscesses, the inclusion of valacyclovir is an intriguing possibility, especially in cases where involvement of herpes virus is suspected. Further clinical research is needed to evaluate the efficacy and safety of using valacyclovir in conjunction with antibiotics. Observing treatment outcomes in patients with potential viral involvement could provide valuable insights.

In this study, we observed suboptimal efficacy of valacyclovir in managing acute apical abscesses. One potential explanation for this finding may stem from the complex interplay between herpes viruses and bacteria, which can contribute to the pathogenesis of the condition. Previous research suggests that viral infections, such as those caused by herpes simplex virus, may alter the immune response and facilitate bacterial colonization, creating a more favorable environment for bacterial pathogens [26]. This interaction could potentially reduce the effectiveness of antiviral therapy like valacyclovir. Although our study did not specifically explore this viral-bacterial interaction, future research could investigate how targeting this interplay might improve treatment outcomes.

The results of the study must be interpreted in the light of the following limitations. First, the sample size was relatively small, which may have limited the statistical power to detect differences between the study groups. Additionally, the study focused exclusively on the use of valacyclovir monotherapy, without exploring combination therapies or alternative antiviral agents. Future research should aim to address these limitations by conducting larger-scale clinical trials with extended follow-up periods. Moreover, investigating the efficacy of combination therapy involving valacyclovir and other antiviral or antibacterial agents may also provide valuable insights into optimizing pain management and reducing recurrence rates in patients with acute apical abscesses. Certain psychological factors, such as anxiety and fear, can significantly influence pain perception and reporting, potentially biasing the assessment of valacyclovir’s analgesic efficacy in this study. Similarly, oral hygiene habits, which affect infection severity and healing, may have varied among participants, influencing the outcomes. In addition, comorbidities like diabetes or immunosuppressive conditions could impair tissue healing and immune responses, further confounding the results. Studies have emphasized the role of these factors in acute apical abscess outcomes, suggesting their omission may limit the generalizability of our findings [27, 28]. Future research should control for or measure these variables to gain a more comprehensive understanding of treatment efficacy. Additionally, investigating the role of host immune modulation and viral-bacterial interactions in the pathogenesis of acute apical abscesses could pave way for novel therapeutic interventions targeting these mechanisms.

5. Conclusions

In this randomized clinical trial, valacyclovir monotherapy did not demonstrate significant efficacy in alleviating postoperative pain compared to standard treatment following emergency chamber opening for acute apical abscesses. Although slight variations in pain scores were observed, the differences were not consistently statistically significant. These findings suggest that valacyclovir alone may not offer substantial pain relief in this context, highlighting the need for further exploration of alternative treatment approaches or combination therapies.

Availability of data and materials

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical concerns.

Author contributions

NF and YSA—conceptualization; writing-original draft preparation. NF and FRQ—methodology. MAA, ZC and HAZ—software; visualization. RJ and MAA—validation; writing-review and editing. MAA and ZC—formal analysis. NF, FRQ, YSA and ZC—investigation. RJ, NF and HAZ—resources. MAA—data curation; funding acquisition. FRQ—supervision; project administration. All authors have read and agreed to the published version of the manuscript.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Dow University of Health Sciences, Karachi (Ref No. IRB-2517/DUHS/Approval/2022/890) on 25 June 2022. Informed consent was obtained from all subjects involved in the study.

Acknowledgment

The authors are grateful to the Deanship of Scientific Research, King Faisal University, Al-Ahsa for facilitating this project.

Funding

This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (KFU250255).

Conflict of interest

The authors declare no conflict of interest.