Analgesic efficacy of corticosteroids and nonsteroidal anti-inflammatory drugs through oral route in the reduction of postendodontic pain: A systematic review.

Analgesic medications in dentistry are indicated for the relief of acute pain, postoperative pain, chronic pain as well as controlling adjunctive intraoperative pain. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has shown an effective reduction of postendodontic pain by action on the cyclooxygenase pathway. Another medication which is used recently is corticosteroid which enables the reduction of pain. They are hormones secreted from the adrenal gland and have strong anti-inflammatory actions. This review aims to compare the analgesic efficacy of NSAIDs and corticosteroids when administered through oral route for reducing postendodontic pain. The secondary objective was to assess the anesthetic effect of the nerve block when an oral premedication of NSAIDs or corticosteroids was administered. The databases of PubMed, ScienceDirect, LILACS, and Cochrane were searched for related topics from 1983 to April 2020. Bibliographies of clinical studies were identified in the electronic search. Clinical studies with postendodontic pain reduction using NSAIDs and corticosteroids were selected. Clinical studies that met all inclusion criteria were reviewed. Data extraction was performed independently by two reviewers. All individuals who administered single dose analgesic (NSAID or corticosteroid) before initiating root canal treatment were taken into inclusion criteria. All the relevant data were extracted from the selected studies were reviewed by two independent reviewers using a standardized data collection form, and in case of disagreement, a third reviewer was enquired to achieve a consensus. Risk of bias of the selected studies was done using Cochrane Risk of Bias Tool (version 1). Mean pain score levels at various time intervals showed an increased analgesic success rate for corticosteroids ( 32-1) in comparison to NSAIDs ( 32-21.4). Anesthetic effect of the nerve block administered was seen to be better when an oral premedication of corticosteroids (38.2%-80.8%) was given in comparison to NSAID (25.5%-73.1%). From the present study, it can be concluded that oral administration of corticosteroids provides a better analgesic efficacy when compared to NSAIDs as an oral premedication for postoperative pain reduction. It can also be concluded that corticosteroids when used as an oral premedication provide a better anesthetic effect of the nerve block administered when compared to NSAIDs given as an oral premedication. These findings could help the clinician determine which pretreatment analgesic would have a better effect in reduction of pain posttreatment as well as increasing the anesthetic efficacy of administered block. Systematic Review Registration Number: CRD42021235394. Copyright:

INTRODUCTION

The primary reason people seek endodontic treatment is for the reduction of tooth pain.[1] In endodontic practice, posttreatment pain is a continuous problem faced by dental professionals. Persistent pain associated with teeth after nonsurgical endodontic treatment has been used as an indicator of treatment failure.[2] Patients who exhibit postoperative pain have shown to be about 80%, with pain levels shown to be moderate-to-severe levels.[3] Pain is a subjective experience and is influenced by various factors such as personality, physical, age, and psychological factors. An individual's ability to cope with pain depends on the individual's resistance to infection, which is varied among different individuals. Postendodontic pain occurs in an individual by stimulation of the various pain receptors. The pain signals are conducted via thin fibers containing unmyelinated C-fibers and myelinated A-δ fibers of primary sensory neurons and secondary order neurons in the spinal cord.[4]

Pain is a subjective experience that is shown to experience in different ways in different individuals. It is seen to have multifactorial sources such as microbial causes, host factors, or mechanical factors.[5] All these factors have a direct influence on the intensity of pain the individual experiences. During the treatment procedure, various factors have a confounding effect on the cause of postoperative pain. For instance, Manfredi et al.[6] came to a conclusion that single-visit and multi-visit endodontic therapies have shown a similar level of pain occurrence posttreatment in individuals and are often done by the operator to reduce chairside time. Pulpal status is one of the crucial factors to be considered during endodontic therapy and is innervated by trigeminal afferent axons.[7] Pain is seen to occur in pulp status diagnosed with symptomatic pulpitis and periodontitis and mostly is seen due to infection origin.[8] This is due to different neuropeptides released when different nerve endings are excited in the tooth such as A-fibers and C-fibers.[9] Intracanal irrigants and medicaments commonly are employed to reduce the microbial load in the canal and are used in conjugation with instrumentation process ultimately providing an inert environment for an effect three-dimensional seal.[10] Sodium hypochlorite (NaOCl) is one of the most commonly used intracanal irrigants and has been shown to influence the postoperative pain levels. Farzaneh et al.[11] in their study evaluated different concentrations of NaOCl for reduction of postoperative pain and came to a conclusion that 5.25% NaOCl was much in reduction of pain in comparison to 2.5% NaOCl. Similarly, intracanal medicaments are also shown to influence postoperative pain levels with double antibiotic paste and calcium hydroxide having similar pain reduction levels in individuals undergoing endodontic therapy.[12]

The major cause of pain for endodontic patients is the release of inflammatory mediators that activate sensory nociceptors surrounding the tooth.[13] Various pathways have shown effective pain reduction by its action on the various pathways present. During this process, chemical mediators are seen to be released at the site such as Toll-like receptors and other inflammatory mediators such as interleukin (IL)-8, IL-6, and IL-1.[14] Cell injury is one of the factors which release pain mediators such as potassium, hydron, histamine, bradykinin, serotonin (5HT), adenosine triphosphate, and nitric acid which act at the variety of receptor site causing the release of arachidonic acid from the cell membranes and metabolized by multiple pathways to a variety of prostanoids.

The use of analgesics has long been used in endodontic practice and is given frequently after an endodontic treatment. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been used by practitioners for a long period of time to relieve pain of patients. These are a heterogeneous group of drugs with analgesic, antipyretic, and anti-inflammatory properties with less known side effects with many of the drugs considered as over-the-counter drugs. Its primary mechanism of action is competitive inhibition of cyclooxygenase (COX) enzyme which is responsible for the transformation of arachidonic acid metabolites which helps in transformation into prostaglandins (PGs) and thromboxane.

COX pathway is divided into two main categories: COX-1 is found in most organs and tissues, whereas COX-2 is selective and found only in response to certain stimuli. The inhibition of these COX-2 receptors has shown a great deal of effectiveness in reducing pain and giving an anti-inflammatory effect without any undesirable side effects.[15] Though this is the preferred mechanism of action for all the NSAIDs. It varies based on the NSAID administered; for instance, aspirin, sodium salicylate, and ibuprofen are shown to inhibit the PG synthesis by inhibition of the arachnoid acid production having a central effect. Paracetamol (acetaminophen) is shown to have centrally acting properties as well as weak inhibitors of both COX-1 and COX-2.[16] Other NSAIDs such as mefenamic acid, diclofenac sodium, and piroxicam (oxicam derivatives) are shown to possess both analgesic and anti-inflammatory effects by acting on both PGs and COX pathway (COX-1 and COX-2). Indomethacin is shown to have sufficient anti-inflammatory effect but analgesic action acting on both COX-1 and COX-2 sites, but its use should be warranted since it is shown to have various adverse effects.[17] Certain NSAIDs are shown to affect only COX sites; for instance, meloxicam is shown to have lesser inhibitory effect on PGs but more on COX pathway, mainly COX-2 than COX-1.[18] Celecoxib and rofecoxib (coxib derivatives) are shown to be selective COX-2 inhibitors only with the same analgesic, antipyretic, and anti-inflammatory action with decreased incidence of side effects such as gastric ulcerations during long-term administration compared to other NSAIDs.[19]

Corticosteroids, on the other hand, have multiple action sites with its primary mechanism, seen to reduce PG synthesis which is responsible for inflammation and reducing vascular permeability. These are considered lipophilic molecules with the ability to cross the blood–brain barrier and have various disadvantages, such as fluid retention. Dexamethasone is the most commonly used corticosteroid for pain reduction, with others being prednisone, and prednisolone can also be used.[20] One of the major advantages of dexamethasone is less fluid retention than other steroids and has less mineralocorticoid effect. Glucocorticoids are hormones which are seen to be released from adrenal glands and can have a side effect.[21] Dexamethasone, prednisone, and prednisolone reduce pain in individuals by acting on the PG synthesis which is responsible for inflammation and pain pathway to form. Steroid receptors are also seen in peripheral receptors and central receptors and are responsible for pain conduction; these are also inhibited by the corticosteroids and hence reduce pain. There is no literature till date which has described about the direct comparison of reduction of postendodontic pain of NSAIDs and corticosteroids when administered through oral route. Hence, this systematic review aims to compare the analgesic efficacy of NSAIDs and corticosteroids consumed through oral route for postoperative pain reduction.

Structured question

Do NSAIDs bring about a better analgesic effect when compared to corticosteroids in the reduction of postoperative pain when taken through oral route?

MATERIALS AND METHODS

This review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO database with registration number CRD42021235394. Detailed search strategies were used for the databases for the identification of studies considered.

A research question was formulated based on the PICO principle: Population: Adult population undergoing endodontic therapy, Intervention: NSAIDs, Comparison: Corticosteroids, and Outcome: Postendodontic pain reduction.

The primary outcome assessment to be done was postoperative pain reduction with NSAIDs and corticosteroids using the Visual Analog Scale (VAS) or Numerical Rating Scale (NRS) at different time intervals. The search databases used were PubMed CENTRAL, LILACS, Google Scholar, and ScienceDirect were searched from 1983 to April 2020 using MeSH words, and all fields with the incorporation of Boolean operators “OR” and “AND” were used for database. The complete search methodology is described in Table 1.

Table 1

Search strategy of all the databases used

Databases	Search strategy
PubMed CENTRAL	“Root canal therapy” OR “Root canal treatment” OR “Symptomatic reversible pulpitis” OR “Symptomatic irreversible pulpitis” OR “Symptomatic apical periodontitis” AND “Aspirin” OR “Aceclofenac” OR “Diclofenac” OR “Indomethacin” OR “Tolmetin” OR “Tenoxicam” OR “Piroxicam” OR “Ibuprofen” OR “Ketoprofen” OR “Naproxen” OR “Mefanamic acid” OR “Niflumic acid” OR “Celecoxib” OR “Metamizol” OR “Paracetamol” OR “Acetylsalicylic acid” OR “Fosfosal” AND “Corticosteroids” OR “Glucocorticoid” OR “Dexamethasone” OR “Prednisonole” OR “Cortisol” OR “Prednisone” OR “Triaminolone” OR Betamethasone) OR “6î±-methyl prednisolone” AND “Pain” OR “Swelling” OR “Postendodontic pain” OR “Pain threshold” OR “Pain measurement” OR “Pain intractable” OR “Oral route”
ScienceDirect	“Root canal therapy” OR “Pulpitis” OR “Apical periodontitis” AND “Aspirin” OR “Diclofenac” OR “Indomethacin” OR “Ibuprofen” OR “Celecoxib” OR “Paracetamol” OR “NSAID” AND “Corticosteroids” OR “Dexamethasone” OR “Prednisone” AND “Pain” OR “Postendodontic pain” OR “Pain reduction”
LILACS	“Endodontic therapy” OR “NSAID” OR “corticosteroid”
Google Scholar	“Endodontic therapy” AND “NSAID” AND “Corticosteroid” AND “Pain reduction”

NSAIDs: Nonsteroidal anti-inflammatory drugs

In addition to this, additional hand searching was done in the following journals: International Endodontic Journal, Journal of Endodontics, Journal of Conservative Dentistry, and Restorative Dentistry and Endodontics. No limiters were applied for the search. Reference lists of the reviews and the identified studies were also checked for possible additional studies. The following criteria were followed.

Inclusion criteria

Randomized clinical trials (RCTs)

Patients of age >15 years indicated for endodontic therapy

Clinical trials in which NSAIDs and corticosteroids have been used as comparative groups and administered directly through oral route

Trials in which root canal treatment was done with diagnosis of symptomatic, asymptomatic irreversible pulpitis, nonvital pulp in single or multirooted teeth

Trials in which pain assessment scale was used such as VAS or NRS for pain evaluation in individuals with intervals up to 2 days

Preoperative pain scores of 2 and above.

Exclusion criteria

Studies in which no placebo group was used

Studies in which incomplete data were seen

Trials in which individuals exhibited with apical periodontitis or periapical abscess.

Data extraction

Data extracted consisted of the following:

Article identification information – authors and publication year

Baseline demographic data – age, sex of participants, and preoperative pulpal status

Study characteristics – sample size, number of visits, and the number of groups

Intervention feature – NSAIDs and corticosteroids

Outcome of interest – postoperative pain scale.

RESULTS

Figure 1 shows the flowchart of the search strategy followed according to the PRISMA guideline. The main finding of this study was to see to reduction of postendodontic pain using NSAIDs and corticosteroids for the reduction of postendodontic pain. Despite the broad time frame search (1985–2020), only recently have the use of corticosteroids been used in endodontics for postendodontic pain reduction. Shahi et al.[22] in 2013 had conducted the first study to clinically administer an oral dose of corticosteroids for the reduction of postendodontic pain. A recent study by Konagala et al.[23] in 2019 was had used orally administered corticosteroid being dexamethasone and deflazacort with piroxicam for the reduction of postendodontic pain. Table 2 denotes the list of included studies based on the strict inclusion/exclusion criteria. Table 3 denotes the summary of the eligible RCT studies, and Table 4 shows the excluded studies with the reason for exclusion. A total of 1719 articles were identified through various databases such as PubMed, LILACS, ScienceDirect, and Google Scholar. The duplicates were excluded, and 58 articles were identified. Out of these 58 articles, they were assessed thoroughly by going through the title and abstract and excluded. A total of 27 articles were selected based on full-text eligibility and were assessed by two independent examiners (J. J and A. P) according to the inclusion and exclusion criteria and were taken into consideration. In case of disagreement, a third reviewer (A. K) was consulted for consensus. From the selected 27 articles, only 5 articles were considered for the qualitative analysis. Each of the articles was assessed independently by two examiners to avoid bias.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of the included studies

Table 2

List of studies included based on criteria selected

Author	Years	Inclusion criteria	Side effects
Kongala et al.[23]	2019	Multirooted posterior teeth - premolar and molar teeth with a diagnosis of vital or nonvital pulp and symptomatic teeth with pulpalgia	No discussion about the possible side effects of the patients
Jorge-Araújo et al.[24]	2018	Single or multirooted teeth with symptomatic/assymptomatic irreversible pulpitis or nonvital teeth that require nonsurgical endodontic therapy	No side effects were reported in any of the medications used
Praveen et al.[25]	2017	Irreversible pulpitis and pulpal necrosis in single-rooted teeth	Gastric issues were developed for patients who consumed corticosteroids with NSAIDs as rescue medication for patients in the corticosteroid group and the patients were informed about it. These subjects were excluded from the study
Bidar et al.[26]	2017	Patients with first and second molar who gave a diagnosis of irreversible pulpitis in cold testing were included in the study	None of the patients reported any side effects of flare-ups after the procedure
Shabi et al.[27]	2013	First and second mandibular molars with asymptomatic irreversible pulpitis and with no periapical pathology	None of the patients reported any side effects up to 48 h

NSAIDs: Nonsteroidal anti-inflammatory drugs

Table 3

Summary of the eligible RCT studies

Authors	Country/sample size/gender	Age of the subjects	Route of administration, dosage, and sample size per group	Local anesthesia (type, dosage)	Study design	Pain reduction assessment and time intervals	Results	Level of significance	Conclusion
Konagala et al.	India, n=132, 62 males, 70 females	18-50 years	Group 1: Oral route-piroxicam-20 mg, Group 2: Dexamethasone-4 mg, Group 3: Deflazacort-30 mg, (n=33 per group)	2% lidocaine with 1:80,000 epinephrine	Double-blinded, parallel randomized, placebo-controlled clinical trial	VAS at time intervals of 6 h, 12 h, 24 h	Pain reduction seen in percentage At 6 h  Dexamethasone (76.6) > piroxicam (70) > deflazacort (60) > placebo (23.3) At 12 h  Dexamethasone (83.3) > piroxicam (83.3) > deflazacort (70) > placebo (30) At 24 h  Dexamethasone (90) > piroxicam (86.6) > deflazacort (76.6) > placebo (43.3) At 48 h  Piroxicam (93.3) > dexamethasone (90) > deflazacort (86.6) > placebo (73.3) At 72 h  Dexamethasone (100) > piroxicam (93.3) > deflazacort (93.3) > placebo (86.6)	Statistically significant difference was seen with placebo group for all drugs up to 24 h (P<0.05)  No statistically significant difference was seen between the groups (P>0.05)	Dexamethasone was seen to be more effective as a pretreatment medication for postendodontic pain reduction followed by piroxicam and deflazacort
Jorge-Araújo et al.	Brazil, n=60	18-66 years	Oral route-ibuprofen-400 mg, dexamethasone-8 mg, placebo (2×1) (n=20 per group)	2% mepivacaine with epinephrine (fraction not stated)	Double-blinded, parallel-randomized clinical trial	NRS at time intervals of 4 h, 8 h, 12 h, 24 h, 48 h	Mean pain levels at different intervals Pretreatment  Placebo (42) > ibuprofen (32) > dexamethasone (29) At 4 h  Placebo (19) > ibuprofen (17) > dexamethasone (9) At 8 h Placebo (17) > ibuprofen (17) > dexamethasone (9) At 12 h  Placebo (16) > ibuprofen (16) > dexamethasone (5) At 24 h  Placebo (14) > ibuprofen (12) > dexamethasone (3) At 48 h  Placebo (8) > ibuprofen (4) > dexamethasone (1)  Anesthetic efficacy was seen to be highest with the following; dexamethasone>ibuprofen>placebo	Pain scores at each time point did not show any statistically significant difference (P>0.05) Anesthetic cartridges did not show any significant difference among all groups (P<0.05)	Dexamethasone was shown to have a better analgesic effect when administered as a premedication for postendodontic pain reduction followed by ibuprofen. The anesthetic efficacy was shown to have better action in participants who had administered dexamethasone
Praveen et al.	India, n=121, 44 males, 42 females	Divided into 3 groups 18-29 years, 31-40 years, 41-50 years	Study group divided into two main categories Irreversible pulpitis, pulp necrosis	2% lidocaine with 1:100,000 epinephrine	Triple-blind, parallel, randomized controlled trial	VAS at time intervals of 6 h, 12 h, 24 h, and 48 h	Mean pain scores at different time intervals At baseline  Ketorolac (40.6) > prednisolone (31.8) > placebo (31.3) At immediate postoperative  Prednisolone (25.9) > ketorolac (23.4) > placebo (23.4)	Statistically significant difference was seen in pain reduction scores among the test groups at 6 h, 12 h, 24 h, and 24 h (P<0.05)	Prednisolone showed an increased analgesic effect when administered as
			Irreversible pulpitis  Oral route-ketorolac-20 mg (n=15), prednisolone 30 mg (n=16 per group), placebo (n=15) Pulpal necrosis  Oral route-ketorolac-20 mg (n=16), prednisolone (n=15), placebo (n=15)				At 6 h Placebo (30.2) > prednisolone (26.7) > ketorolac (20.6) At 12 h  Placebo (32.03) > ketorolac (30.4) > prednisolone (17.5) At 24 h  Ketorolac (27.1) > placebo (26.5) > prednisolone (14.6) At 48 h  Ketorolac (21.4) > placebo (20) > prednisolone (9.3)	a premedication analgesic for postendodontic pain reduction compared to Ketorolac
Bidar et al.	Iran, n=78, 30 males, 48 females	Divided into 2 groups 20-45 years, 45-60 years	Oral route-ibuprofen-400 mg, dexamethasone-4 mg, placebo (n=26 per group)	1.8 ml of 2% lidocaine with 1:80,000 epinephrine	Randomized, double-blind, placebo-controlled study	VAS used to assess up to 48 h	Success rate of the blocks administered Dexamethasone (80.8%) > ibuprofen (73.1%) > placebo (38.5%)	Statistically significant difference was seen among the test groups for the IANB block administered (P<0.05)	Dexamethasone when administered as a premedication showed a better anesthetic effect for the IANB nerve block administered compared to ibuprofen
Shabi et al.	Iran, n=165	Patients below 18 years were excluded	Oral route-400 mg ibuprofen-400 mg, Dexamethasone-0.5 mg (n=55)	1.8 ml of 2% lidocaine with 1:80,000 epinephrine	Randomized, double-blind study	100 mm VAS was used to assess pain reduction up to 48 h	Success rate of the blocks administered Dexamethasone (38.2%) > ibuprofen (25.5%) > placebo (12.7%)	Statistically significant difference was seen among the success rate of IANB administered within the group (P<0.05)	Dexamethasone showed a better analgesic efficacy compared to all other study groups. The anesthetic effect of the block administered was seen to more effective when a premedication of dexamethasone was administered compared to ibuprofen

VAS: Visual Analog Scale, NRS: Numeric Rating Scale, IANB: Inferior alveolar nerve block

Table 4

List of studies excluded based on the criteria

Author	Years	Reason for exclusion
Romina Brignardello-Peterson[15]	2017	The study is a review of study done by Praveen et al. which is included in this systematic review
Menhinick et al., Litwoski et al., Attar S et al., Mehrvarzfar P et al.	2009	The study is a collection of mini reviews consisting of various studies and none of the included studies satisfy the inclusion criteria
Barron RP et al.	2004	Although the study had both the inclusion criteria groups, it was used for evaluating third molar extractions
Gallatin E et al.	2000	The study did not follow the inclusion criteria since it did not use corticosteroids and NSAIDs as 2 separate groups. The study has not mentioned about endodontic therapy completion been done
Torabinejad M et al.	1994	This prospective study did have NSAIDs, acetaminophen, ibuprofen, and ketoprofen as separate groups. Though it had a separate corticosteroid group it was used in conjugation with penicillin or a placebo
Ligia Nadal Zardo et al.	2013	The randomized parallel double-blind clinical trial though used etoricoxib and dexamethasone as the groups. The use of these analgesics was used for mucogingival surgery pain reduction
Nagendrababu V et al.	2019	The study is a systematic review and is excluded
Bahcall JK et al.	2003	The study did not satisfy the inclusion criteria and was excluded
Bahammam MA et al.	2017	It included both the dexamethasone and ibuprofen group but was used to control postsurgical implant placement
Shantiaee Y et al.	2017	It did not satisfy the inclusion criteria of this study
Fuller M et al.	2018	The double-blinded study only used oral methylprednisolone as a study group with the second group to be placebo
Kan E et al.	2016	The study was used for periapical microsurgery and also consisted of only a single group consisting of dexamethasone
Aminoshariae A et al.	2016	This is a systematic review and was excluded
Lapidus D et al.	2016	This is a systematic review and was excluded
Hatton J et al.	2015	It did not satisfy any inclusion criteria and was excluded
Regalado et al.	2014	It did not satisfy any inclusion criteria and was excluded
Paschoalino et al.	2012	This study was a case report and was excluded
Bahcall JK et al.	2003	The study did not satisfy any inclusion criteria and was excluded
Torabinejad M et al.	1994	The study did not satisfy the inclusion criteria and postoperative pain was assessed after the instrumentation
Trope M et al.	1990	The study did not satisfy the inclusion criteria and thus was excluded
Rogers et al.	1990	Though this study had 2 separate groups of NSAIDs and corticosteroids they were used as an intracanal medicament which did not satisfy the inclusion criteria
Romundstad et al.	2007	The study though used glucocorticoids and NSAIDs on postoperative pain control, it was used for breast surgery and did not include in the criteria

NSAIDs: Nonsteroidal anti-inflammatory drugs

Risk of bias

The risk of bias of all the included studies[2223242526] was assessed these assessed using the Cochrane risk of bias assessment tool.[27] This tool was used since it is shown to have a high sensitivity rate and is shown to give a comprehensive method to assess the potential risk of bias, especially in randomized control trial studies.[28] From the included studies, seven domains were assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, attrition bias, reporting bias, and any other bias which could affect the results of the study. In the assessment, Jorge-Araujo et al.[24] showed an overall good quality since it satisfied all the assessed domains and overall considered to have a low risk of bias whereas Konagala et al.[23] showed an overall poor quality since it had more than two assessed domains in high bias. Rest most of the studies were classified as unclear bias. The risk of bias summary and graph was generated using Review Manager 5 software (Cochrane, London).

Figure 2 shows the summary of the risk of bias of the included studies, and Figure 3 shows the graph for risk of bias assessment. Table 5 shows the risk of bias based on the major criteria, and Table 6 shows the risk of bias based on the minor criteria. Randomization of all the participants in the included studies were discussed with significant detail with the evaluation methodology of sample size mentioned. Allocation concealment is a methodology to prevent selection bias among the study groups and was discussed with detail in three of the five included studies.[232425] None of the included studies mentioned any methodology error which could affect the results of the study. Blinding is an important feature of RCTs which could minimize bias as well as maximize the validity of the results achieved from the study.[29] In regard to blinding procedure followed, three of the five included studies[242526] explained with sufficient detail. The remaining two studies did not provide data if the operators treating patients were blinded on which analgesic was administered to the patients. Dropouts of the participants is a crucial factor to be considered and have a detrimental role on the results achieved from the study. Only three out the five included studies discussed about dropouts of the participants with significant detail.[232425]

Figure 2

Risk of bias assessment – Summary

Figure 3

Risk of bias assessment – Graph

Table 5

Risk of bias - Major criteria

Author	Randomization	Allocation concealment	Assessor blinding	Dropouts described
Konagala et al., 2019	Yes	Yes	No	Yes
Jorge-Araújo et al., 2018	Yes	Yes	Yes	Yes
Praveen et al., 2017	Yes	Yes	Yes	Yes
Bidar et al., 2017	Yes	Yes	Yes	No
Shabi et al., 2013	Yes	No	No	No

Table 6

Risk of bias - Minor criteria

Author	Sample justified	Baseline comparison	I/E criteria	Method error
Konagala et al., 2019	Yes	Yes	Yes	No
Jorge-Araújo et al., 2018	Yes	Yes	Yes	No
Praveen et al., 2017	Yes	Yes	Yes	No
Bidar et al., 2017	No	Yes	Yes	No
Shabi et al., 2013	Yes	Yes	Yes	No

DISCUSSION

Pain management is a fundamental aspect to be considered during the treatment of endodontic pain and is vital for the operator to control this for successful endodontic therapy. The assessment of pain is a critical factor in all these studies with various pain scales present to analyze the degree of pain experienced by the patients for the endodontic procedure, such as the NRS, Verbal Rating Scale, and VAS. Most of these scales are verbally or graphically delivered and have different scale ranges.[30] Jensen[31] showed the use of VAS for assessment of pain. It is most commonly used as a 100-mm line with verbal descriptors ranging from “no pain” to “worst imaginable pain.” Many researchers advocate using VAS and NRS because of its greater sensitivity and are highly reproducible, unaffected by any gender, and are much simpler for the patients to use with its failure rate seen to be 4%–11%.[32] From the included studies, all the studies[2223242526] have used the VAS for pain assessment except for Jorge-Araújo et al.,[24] who used NRS for the assessment of pain. Some studies[222326] have done a preassessment of pain using the pain assessment scale, and the other studies[2425] have only done a postendodontic pain evaluation.

In the present review, two out of five included studies[2425] had an overall “low” risk of bias with all domains assessed being under low risk. Bidar et al.[26] and Shahi et al.[22] showed an overall “unclear” bias with allocation concealment, blinding, and outcome data not explained with adequate detail in their study. Kongala et al.[23] showed an overall “high” risk of bias since domains such as random sequence generation, allocation concealment, and blinding of participants and personnel were not mentioned adequately considering them as high risk. Overall, most of the studies showed a low risk, and the results of this study can be followed to an extent.

The use of pretreatment analgesia for postendodontic pain is a well-quantified method with numerous studies, proving that pretreatment analgesia has shown a significant decrease in postendodontic pain preoperatively compared to administration postoperatively.[33] Oral prescription of analgesics is the most commonly used method since it is clinically useful and convenient for the patient and the researcher than other modes of administration, such as intramuscular/intravenous injection.[34] All the included studies have used only oral analgesics at various times, followed by which pain assessment was done. NSAIDs for conditions such as irreversible pulpitis have been shown to reduce inflammatory mediators such as PGE2, which has an overall effect in the reduction of postendodontic pain.[35] The first use of corticosteroids in endodontics is by intracanal administration of corticosteroids for pain reduction.[36] Pochapski et al.[37] had initially used an oral administration of corticosteroids as a pretreatment analgesic which had shown to have a significant reduction of postendodontic pain compared to the placebo group. Followed by this study, various authors had different groups to assess the analgesic efficacy of corticosteroids. All the included studies have followed the protocol of administration of pretreatment analgesia.[2223242526] However, the time interval of the administration of the analgesic varied for different authors who could have an effect on the pain score given by the subjects of the study, with all the subjects in all the studies reporting a better tolerance and pain reduction postendodontic treatment after pretreatment analgesic administration.

All the included studies had done a pulp sensibility testing before the endodontic treatment procedure. The different pulp sensibility testing used are cold tests, heat tests, electric pulp testing, test cavity preparation, and local anesthetic test.[38] The most advocated pulp testing method employed by practitioners is cold testing which is ideally done in conjugation with electric pulp testing for accurate results and used to differentiate between reversible and irreversible pulpitis. This is due to the stimulation of the Aδ nerve fibers within the pulp dentinal complex.[39] It is an inexpensive test and used by many clinicians in conjugation with electrical pulp testing. In the present study, most of the authors[22242526] have used cold test to assess the pulpal status of the tooth with some studies using electrical pulp testing for the confirmation of the assessment.[2425] Konagala et al.[23] though had made a pulpal diagnosis for the assessment of pulpal status; the method of assessment has not been mentioned since the thermal tests used are seen to give different response perceptions for the patients.[40] Although their study had combined clinical examination, radiographic findings, and dental history, no mentioning of the thermal test used could have an influence on the selection of the samples and was considered as a bias in our evaluation.

The use of NSAIDs has long been advocated for management of endodontic pain. There are some instances in which the patients have reported side effects such as GI disorders and cardiovascular problems on long-term usage.[41] This, however, did not inhibit the use of NSAIDs for these patients since the side effects exhibited are quite negligible. The use of corticosteroids has shown a high anti-inflammatory action by reduction of the release of arachidonic acid by inhibiting the action of phospholipase-A2.[42] Isett et al.[43] had proven that reducing inflammatory mediators such as PGE2 and IL-8 seen only in cases of irreversible pulpitis had reduced after the administration of corticosteroids. Although it has high inflammatory action, the side effects of the use of corticosteroids are common. Some of them being gastrointestinal bleeding, insomnia, and proximal muscle weakness[44] should not be used continuously for long periods. Even with all these side effects, the usage of corticosteroids as an analgesic has not been hindered since its usage is not limited to a single-frequency consumption. Instead, multiple frequencies of consumption by the same individual show increased side effects. One of the significant factors to be taken notice of is the increased chances of gastric ulcers, as reported by Piper et al.[45] by the drug interaction between corticosteroids and NSAIDs. In spite of this, none of the included studies had patients reported with a problem even after administration of rescue medication.

Two of the included studies by Shahi et al.[22] and Bidar et al.[26] though used NSAIDs and corticosteroids as a premedication, the primary outcome of both the studies was to evaluate the anesthetic efficacy of the inferior alveolar nerve block nevertheless these articles were considered since it followed all the inclusion/exclusion parameters.

The administration of an oral premedication of an analgesic has a direct effect on the anesthetic effect of the nerve block administrated as reported by the included studies in this review. The two included studies[2226] followed all the inclusion criteria of the present study though the primary outcome of these studies was to assess the success of the administered nerve anesthetic block. It has been reported that the success rate of nerve blocks decreases by several factors such as anxiety and is drastically decreased in the case of irreversible pulpitis.[46] This is due to the nociceptors by inflammatory mediators such as PGs, which decrease the anesthetic effect of the administered drug.[47] From the included studies, corticosteroids have shown to have a better success rate when administered as an oral premedication than NSAIDs showing a 30% increased success rate when compared to an oral premedication of NSAIDs. The anesthetic efficacy of the nerve block administered was significantly improved when an oral premedication of corticosteroids was given in comparison to NSAIDs.

CONCLUSIONS

Most of the studies in the present review showed an overall “low” and “unclear” risk; it can be concluded that oral consumption of corticosteroids has a better analgesic effect when compared to NSAIDs. Although the onset of action of NSAIDs is much better than when compared to corticosteroids, the analgesic effect produced by corticosteroids has a sustained effect for an extended period producing a better analgesic effect. Oral premedication of corticosteroids has a better anesthetic efficacy when compared to NSAIDs. One of the limitations for this review is the number of studies included. The inclusion of studies satisfying the inclusion criteria was limited. It is necessary to do more drug efficacy clinical studies, which can show much better results on the analgesic efficacy of NSAIDs and corticosteroids in postendodontic pain reduction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.