Comparative Efficacy of Analdent (Herbal Analgesic Preparation) and Aceclofenac on Pain Intensity After Tooth Extraction: A Split-Mouth Randomized Clinical Trial

Abstract

Background and Aim

Pain management following tooth extraction is crucial in minimizing patient suffering and risk of infection and hastening the recovery. Safety issues with routinely prescribed drugs such as NSAIDs for pain management call for search of an effective and safe alternative. Advances in the field of alternative medicine have led to the use of various natural products for pain management in the field of dentistry. The aim of the study was to compare the efficacy between the analdent and aceclofenac in terms of alleviation of post-operative pain and facial swelling after extraction of tooth.

Methods

A split-mouth randomized clinical trial was conducted on 22 participants in the age range of 13–25 years requiring extraction of first permanent premolars for orthodontic reason. The extraction sites were randomized to receive either analdent or aceclofenac post-orthodontic extraction. Post-extraction dental pain was assessed after 8 h, 24 h, 48 h and 72 h post-operatively using a visual analog scale, and incidence of swelling was recorded.

Results

Pain score showed a significant reduction (p = 0.001) post-operatively within analdent (herbal drug) group as well as Zerodol (aceclofenac) group. However, there was no significant difference in pain intensity between the two groups at each interval. Two participants in analdent group and one participant in aceclofenac group reported swelling after 8 h of extraction which subsided after cold pack application.

Conclusion

Analdent was found to be equally effective as aceclofenac in managing pain after the tooth extraction with relatively no side effects.

CTRI Registration Number: CTRI/2020/ 03/024296 dated 27/03/2020.

Introduction

Dental extraction is a one of the most common oral surgical procedures in dental practice. The major concern after every extraction is post-operative pain and swelling. The quality of life after extraction is affected more in patients with pain or swelling alone or in combinations [1]. Despite existence of numerous studies, no analgesic has claimed the certificate of merit, and the quest is still on to find a better agent in this aspect. Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed by the dentists for lessening pain following tooth extraction [2]. Aceclofenac, a drug from NSAIDs family, is routinely prescribed analgesic for pain after extraction. It shows anti-inflammatory and analgesic properties. It hinders the activity of cyclooxygenase enzyme system, thus reducing the biosynthesis of prostaglandins [3]. However, NSAIDs have certain limitations and are contraindicated in peptic ulcer, asthma, nasal polyps, cerebrovascular diseases [4–7]. NSAIDs are also known to have nephrotoxic activity [8].

In the light of these limitations, search for a suitable alternative for analgesics to reduce post-extraction dental pain has led to the discovery of medicinal products which are effective and safe. Analdent, a herbal preparation, is an anti-inflammatory, analgesic, and antimicrobial medicine having no side effects [9]. This drug has undergone preclinical and clinical testing at Bharati Vidyapeeth College of Pharmacy, Kolhapur, and Tilak Ayurved Mahavidyalaya, Pune, respectively [9]. The product was found to be appropriate for all age-groups without any untoward results. It is safe for both gastrointestinal tract and kidney [9]. However, the literature showing analgesic efficacy of Analdent post-dental extraction is limited. Hence, the present study was done to compare the efficacy between the analdent and aceclofenac in terms of alleviation of post-operative pain and facial swelling after extraction of tooth. Null hypothesis states that there is no difference in the efficacy of the analdent and aceclofenac in terms of alleviation of post-operative pain and facial swelling after the extraction of tooth.

Material and Methods

Study Design and Study Setting

This randomized parallel clinical trial involved a split-mouth design that was carried out on 22 participants in the Department of Oral and Maxillofacial Surgery. Protocol of the study was designed and implemented considering the Declaration of Helsinki—ethical principles for medical research involving human subjects, and was approved by the Institutional Ethical Committee [BV(DU)MC&H/Sangli/IEC/D-24/19]. The trial was registered prospectively with Clinical Trial Registry—India (CTRI No. CTRI/2020/ 03/024296). Written consent was obtained from subjects who were 18 years of age and above after informing them about all the procedures and possible discomfort. Written informed consent was obtained from the parents of those subjects who were less than 18 years of age. Entry of the participants in the study was voluntary, and they were allowed to exit the study any point of time.

Study Participants

The study was conducted on 22 participants, within the age group of 13–25 years in the Department of Oral and Maxillofacial Surgery. These participants required non-surgical extraction of bilateral maxillary or mandibular premolar for orthodontic treatment. Considering the split-mouth nature of the study, the extraction sites within each participant were randomly assigned to two groups to receive:

• Group 1: 22 extraction sites receiving Zerodol [aceclofenac 100 mg tablet, ICPA laboratories Ltd, India] twice a day post-orthodontic extraction for 3 days

• Group 2: 22 extraction sites receiving analdent tablet [M/S Milind Chemicals and Marketing Corporation, Miraj, India] twice a day post-orthodontic extraction for 3 days

Composition of analdent Tablet (Fig. 1)

Fig. 1.

Flow chart of the study

Clove Powder (Eugenia caryophyllus) Ayu Ph 200 mg; Ringni fruit powder (Indicum xanthocarpus) Ayu Ph 50 mg; Hirda powder (Terminalia chebula) Ayu Ph 50 mg; Cardamom (veldoda) seed powder (Elettaria cardamomum) Ayu Ph 15 mg; Ginger (Suntha) powder (Elettaria cardamomum) Ayu Ph 10 mg; Babool bark powder (Acacia arabica) Ayu Ph 50 mg.

Inclusion Criteria

Subjects aged between 13 and 25 years and in need of the extraction of healthy premolar tooth for orthodontic reasons were included.

Exclusion Criteria

Medically compromised participants, participants with history of allergy to NSAIDs, participants suffering from ulceration or those on medication within the past 6 months, participants with systemic conditions such as cardiovascular diseases, diabetes mellitus, gastrointestinal lesions, and bleeding disorders, participants having either systemic or dental infection, participants not willing to undergo dental extraction and participants not willing for follow-up post-operatively were excluded.

Sample Size

Sample size for the study was established by considering an effect size of 1.48 with α = 0.05 and a power level of 0.95 for the variable pain [9]. On the basis of these values, a minimum sample size of 12 extraction sites per group was calculated to be necessary. Considering the possibility of attrition during the follow-up sessions, 22 participants were finally included.

Randomization and Blinding

Participants who fulfilled the inclusion criteria were included, and their extraction sites were randomly assigned to one of the study groups. Randomization was achieved employing lottery technique by a person who was not the part of the study. The examiner, who assessed the pain score, was blinded regarding the group allocation. Participants were kept blind regarding the intervention by giving them the medicines in same size and colored containers. The person, who analyzed the data, was also kept blind regarding the patient allocation to the intervention.

Intervention and Measurements

All the participants included in the study had a healthy periodontium and with no extensive decay in their teeth. On the day of the appointment, the particular tooth was extracted by non-surgical extraction method, also known as closed method of extraction, under local anesthesia (2% lignocaine with 1:80,000 adrenaline). A time limit of 30 min was recommended for each participant. Either right maxillary or mandibular first premolar was extracted in the first appointment employing a standard operating procedure. The post-extraction instructions were given, and the participants were asked to contact the primary investigator in case of emergency. The participants were prescribed with allocated analgesic medication and were instructed about the dose of the drug. The patients were instructed to carry the drug container during every follow-up visit to ensure patient’s compliance to prescribed interventional medications. Pain intensity and swelling were recorded after 8 h of extraction, 24 h of extraction, 48 h of extraction and 72 h of extraction. A visual analog scale (VAS) was used to assess the pain intensity after extraction of the tooth. Participants were asked to assess and rate the pain in the range of 0 (no pain) to 10 (worst possible pain); VAS was categorized as: 0 = No pain; 1–3 = mild pain; 4–6 = moderate pain; 7–9 = severe pain; and 10 = worst pain possible. A period of 10 days was given to allow for the complete elimination of the drug from the body, and the participants were recalled for next contra-lateral premolar extraction. Left maxillary or mandibular first premolar was then extracted and prescribed with other groups of analgesic medication and was again asked to assess and record the intensity of the pain after 8 h of extraction, 24 h of extraction, 48 h of extraction and 72 h of extraction. Swelling was reported as present or absent. All the extractions were carried out by a single trained Oral and Maxillofacial Surgeon. At the end, 22 participants reported with VAS report and were included for final analysis.

Statistical Analysis

The data obtained were compiled and analyzed using Statistical Package for the Social Sciences (SPSS) v20. Level of significance was kept at 5%. Pain intensity within each group at different intervals was compared using Repeated Measure ANOVA test followed by post hoc test for pairwise comparisons. Pain intensity between two groups was compared using independent t test. Phenomenon of swelling was reported using frequency and percentage.

Results

Figure 1 shows the flow of the study design. Table 1 shows the demographic details of study participants at baseline. Out of 24 participants, two participants did not report during follow-up appointments and 22 participants completed the study. Mean age of the participants was 18.23 years with 13 male and 9 female participants comprising the study population. Table 2 shows the comparison of change in VAS score within analdent group and aceclofenac group. VAS score showed a significant reduction (p = 0.001) post-operatively within analdent group as well as aceclofenac group. VAS score in analdent group after 8 h was 5.95 which was reduced to 0.86 after 72 h. Similarly, VAS score in aceclofenac group after 8 h was 5.914 which reduced to 1.18 after 72 h. A within-group comparison showed a statistically significant difference within different time intervals in both groups (p < 0.05).

Table 1.

Demographic details of study participants

	Mean ± SD
Age	18.23 ± 2.76
Gender N (%)
Male	13 (59.10)
Female	9 (40.90)

Table 2.

Evaluation of change in VAS score within analdent group and Zerodol group

Group	8 h	24 h	48 h	72 h	F value	p value
Analdent	5.95 ± 3.11a	3.50 ± 2.35b	1.86 ± 1.78c	0.86 ± 1.70d	53.590	0.001*
Aceclofenac	5.14 ± 3.04e	3.23 ± 2.16f	2.05 ± 1.65 g	1.18 ± 1.59 h	44.703	0.001*

Repeated measure ANOVA test

*Indicates significant difference at p ≤ 0.05; different superscript letters within each row show significant difference among different time intervals within each row

Table 3 shows the intergroup comparison of pain intensity at each time interval between both the groups. Intergroup comparison showed no significant difference in pain intensity between both the groups for each time interval tested (p > 0.05). Apart from pain intensity, the presence or absence of swelling was also evaluated among study participants. Two participants in analdent group and one subject in aceclofenac group reported swelling after 8 h of extraction which subsided after cold pack application. None of the study participants reported swelling after 24 h, 48 h and 72 h of extraction.

Table 3.

Intergroup comparison of VAS score at each interval among both the groups

Interval	Group	N	Mean	Difference	t value	p value
8 h	Analdent	22	5.95 ± 3.11	0.81	0.882	0.383 (NS)
	Aceclofenac	22	5.14 ± 3.04
24 h	Analdent	22	3.50 ± 2.35	0.27	0.401	0.690 (NS)
	Aceclofenac	22	3.23 ± 2.16
48 h	Analdent	22	1.86 ± 1.78	− 0.19	− 0.352	0.727 (NS)
	Aceclofenac	22	2.05 ± 1.65
72 h	Analdent	22	0.86 ± 1.70	− 0.32	− 0.641	0.525 (NS)
	Aceclofenac	22	1.18 ± 1.59

Independent t test; NS non-significant

Discussion

In any oral surgical procedure, the major challenge for clinicians is to manage the post-operative pain. There are several surveys which report that pain because of dental surgical procedure is the major obstacle for the utilization of dental services by people [10]. Therefore, pain management is always the high priority topic of research in Oral and Maxillofacial Surgery [11]. In this study, we have tested a new herbal product analdent against the routine NSAID aceclofenac in post-operative management after tooth extraction.

The results of this study revealed that both drugs significantly reduced the pain over a period of time. But there was no significant difference observed between the two groups in relation to pain management. This indicates that both the drugs are equally effective in managing the pain post-tooth extraction. There are no similar research reports on analdent efficacy for direct comparison of our study findings. However, in recent times, several herbal products have shown potential to reduce the post-operative pain. A study conducted by Sukumaran A et al. to assess the effect of herbal patch in combination with oral analgesics in reducing pain following tooth extraction compared to routine analgesic drugs alone showed that combination of herbal patch and oral analgesic was more effective in pain control than oral analgesics alone [12]. The possible reason for significant difference in this previous study might be attributed to the use of combination of herbal patch and oral NSAID drug as compared to herbal drug alone in the present study. Another study that evaluated the efficacy of topical aloe vera application in healing and pain control in atraumatic dental extractions showed a significant reduction in pain in aloe vera group as compared to oral analgesic group [13]. Other herbal products such as honey, PowerStrips (Proprietary blend of herbs), neem, and curcumin have shown efficacy in managing pain post-tooth extraction [14–16].

The growing trend in the research literature toward alternative drugs reflects that there is a need for better analgesics and anti-inflammatory drugs for post-extraction pain management. There has been a huge upsurge in the use of herbal medicines in recent times. In developing nations, people prefer them mainly due to cost factor, cultural acceptability and easy availability. In developed nations, they are mostly preferred over allopathic counterparts as they are assumed to be relatively safer than allopathic drugs. Analdent, a herbal medicine, is a mix of herbs that has analgesic as well as antimicrobial properties [9] (Fig. 2). Prime ingredient of analdent is clove powder which is known to have analgesic or anti-inflammatory effect due to the presence of eugenol that shows anti-nociceptive action [17, 18]. This analgesic activity of clove might be attributed to inhibitory action of eugenol on voltage-gated sodium and calcium channel currents and action on P2X_3, a pain receptor expressed in the trigeminal ganglion [19]. Ringni fruit is also known to possess anti-inflammatory properties due to the presence of solasodine which is used for the production of steroidal drugs in pharmaceutical industries [20]. Solanum species have been reported to contain various alkaloids, saponins, sterols, flavonoids and their glycosides, tannins, gums [21]. Analgesic action of Solanum extract might be attributed to the inhibition of the production and release of prostaglandins or blocking their receptors [21]. Another ingredient present in analdent tablet, Ginger, is also known to have anti-inflammatory action due to the presence of gingerol, shogaol, and other structurally related substances [22, 23]. These constituents in ginger are responsible for annihilation of 5-lipoxygenase or prostaglandin synthetase that results in inhibition of prostaglandin and leukotriene biosynthesis. They are also responsible for inhibition of synthesis of pro-inflammatory cytokines such as IL-1, TNF-α, and IL-8 [24, 25]. Cardamom, another ingredient, has shown analgesic effects in animal models which is related to the presence of 1,8-cineole and the other terpenoids [26]. Aqueous extracts of Hirda fruit (T. chebula) are known to possess anti-inflammatory properties by inhibiting COX-1, COX-2, 5-LOX, TNF-alpha and downregulating NFkB [27]. Another ingredient, Babool, is very rich in secondary metabolites such as alkaloids, tannins, terpenes, flavonoids, and fatty acids. These metabolites show anti-inflammatory effect [28].

Fig. 2.

Analdent tablet

This study has certain limitations which have to be taken into consideration while generalizing the findings. Patients requiring extraction for orthodontic treatment were included, and hence, study findings cannot be generalized to infected teeth extractions. The patients were selected from a single hospital which may not be the representative sample. There is a high scope for future research on testing analdent in different populations, in different oral and maxillofacial surgical procedures and comparison with different drugs. If this drug shows consistent efficacy in many more clinical trials, then it can be prescribed for the management of dental pain.

Conclusion

This study has shown that the herbal product analdent is equally effective as aceclofenac in managing pain after the tooth extraction. Besides that, analdent has not shown any serious side effects. This drug can be prescribed for dental pain management if future research confirms its efficacy.

Author’s Contribution

All authors contributed to the study conception and design. Material procurement, clinical procedures and data collection were performed by SS, SK and HK. Data analysis was performed by MK and UW. The first draft of the manuscript was prepared by MK, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

None.

Availability of Data and Material

Will be provided on request.

Declarations

Conflict of interest

The intervention drug analdent was supplied by M/S Milind Chemicals and Marketing Corporation.

Ethics Approval

Approved by Institutional Ethical Committee.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.