Educational aims and objectives
This clinical article aims to compare the effect of preoperative administration of single-dose ketorolac, a non-steroidal anti-inflammatory drug and placebo on postoperative pain in teeth with irreversible pulpitis and apical periodontitis.
Endodontic Practice US subscribers can answer the CE questions by taking the quiz to earn 2 hours of CE from reading this article. Correctly answering the questions will demonstrate the reader can:
- Identify some previous studies regarding the management of postoperative pain.
- Realize that there is a strong relationship between pulp status and postoperative pain and therefore a need to identify methods to alleviate that pain.
- Compare the effect of preoperative administration of single-dose ketorolac with a NSAID and placebo on postoperative pain in teeth with irreversible pulpitis and apical periodontitis.
- Discover that a single dose of ketorolac is as effective or as safe as NSAID for the relief of pain after operations on postoperative pain in teeth with symptomatic apical periodontitis.
Drs. Jorge Paredes Vieyra, Fabian Ocampo Acosta, and Francisco Javier Jiménez Enriquez compare the effect of preoperative administration of single-dose ketorolac, a non-steroidal anti-inflammatory drug and placebo on postoperative pain in teeth with irreversible pulpitis and apical periodontitis
Dental pain is a multifaceted process that is partially comprised of biological, biochemical, environmental, and psychogenic factors. Several factors can influence clinicians’ decisions to recommend analgesics in helping combat their patients’ postoperative pain. It is well recognized that, in general, preoperative pain is the principal factor in determining the level of postoperative pain (Sessle, 1986).1 Prevention and control of pain in endodontic treatment is an important issue (Cunningham and Mullaney, 1992).2
Pain is conceptualized as a complex sensation, and odontogenic pain is a multi-dimensional experience that involves sensory responses and cognitive, emotional, conceptual, cultural, and motivational aspects (Sessle, 1986).1 The incidence of postoperative pain of mild intensity is not an occasional event even when endodontic treatment has followed suitable standards (Arias, et al., 2013).3 This usually comprises acute pain, meaning the correct treatment can be rapidly applied.
Mild pain after chemo-mechanical preparation can develop in about 10%-30% of the cases (Siqueira, et al., 2002),4 and in most instances, the patient can bear the discomfort or can make use of common analgesics, which are usually effective in relieving symptoms.
Although ketorolac is a contentious drug in Europe, with the EU split over its safety, the authors have embarked on a comprehensive review of its efficacy in dentistry.
Development of acute or severe pain, accompanied or not by swelling, has been demonstrated to be an unusual occurrence. However, these circumstances usually constitute a true emergency and very often require an unscheduled visit for treatment (Pak and White, 2011).5 The management of postoperative pain has been the subject of many research studies, including preoperative explanations and instructions (Sathorn, Parashos, Messer, 2008),6 long-acting anesthesia (Parirokh, Yosefi, and Nakhaee, 2012),7 the glide path (Pasqualini, Mollo, and Scotti, 2012),8 occlusal reduction (Parirokh, Rekabi, and Ashouri, 2013; Rosenberg, Babick, and Schertzer, 1998),9,10 medication using salicylic acid (Morse, Esposito, and Furst, 1990),11 non-steroid anti-inflammatory drugs (NSAIDs) (Attar, Bowles, and Baisden, 2008),12 combination of ibuprofen and acetaminophen (Menhinick, Gutmann, and Regan, 2004),13 narcotic analgesics (Ryan, et al., 2008),14 a combination of narcotic analgesics with aspirin (Morse, 1987)15 or acetaminophen (Sadeghein, Shahidi, and Dehpour, 1999),16 and steroidal anti-inflammatory drugs (Pochapski, et al., 2009).17
Pain perception is a highly subjective and variable experience modulated by multiple physical and psychological factors, and pain reporting is influenced by factors other than the experimental procedure (Bender, 2000).18 The extrusion of microorganisms or debris during endodontic treatment results in inflammatory response and inflammation (Oliveira, 2011).19 A recent systematic review showed that between 3% and 58% of patients were reported to have experienced endodontic postoperative pain (Sathorn, Parashos, Messer, 2008).6
Activation of nociceptive sensory nerve fibers may also be related to concentrations of inflammatory mediators like histamine (Dale and Richard, 1918).20 Also, histamine, an inflammatory mediator, is capable of sensitizing and activating nociceptive sensory nerve fibers (Hargreaves, et al., 1994).21
The management of pain is a critical and challenging part of dentistry, as pain is a major postoperative symptom after many dental procedures. There are various analgesics and techniques; patients want the best for managing their pain, and clinicians need to know them. Knowing how well an analgesic and technique works and its associated adverse effects is fundamental to clinical decision-making (Cunningham and Mullaney, 1992).2
The incidence and severity of postoperative pain are associated with specific dental treatments; the highest is with root canal therapy (Levin L, Amit A, Ashkenazi, 2006).22 Postendodontic pain, particularly after initial endodontic therapy, should ideally be eliminated by the therapy; however, analgesics are frequently required to diminish pain (Cunningham and Mullaney, 1992).2 There is a strong relationship between pulp status and postoperative pain, influencing the experience of pain, which may undermine the patient’s confidence in the procedure and the clinician (Arias, et al., 2013).3 Ketorolac is an excellent acting analgesic used widely in surgery and medicine (Grond and Sablotzki, 2004).23
In dentistry, there have been several studies that used a single dose of ketorolac associated with tramadol for control of pain mainly in operations on the third molars. However, its analgesic efficacy is controversial, with reports that its effect is similar (Mishra and Khan, 2012)24 or less good (Desjardines, et al., 1998)25 that that of non-steroidal anti-inflammatory drugs (NSAID). According to these studies, a single dose of tramadol has some relatively common adverse effects (Shah, et al., 2013).26 The purpose of this study was to compare the effect of preoperative administration of single-dose ketorolac, a non-steroidal anti-inflammatory drug and placebo on postoperative pain in teeth with irreversible pulpitis and apical periodontitis.
Materials and methods
The institutional review board of the Facultad de Odontología Tijuana México approved the study protocol, and all the participants were treated in accordance with the Helsinki Declaration (www.cirp.org/library/ethics/helsinki). The study started in February 2016 and ended in March 2017. The main inclusion criteria were a) a diagnosis of pulpitis confirmed by positive response to hot and cold tests and b) clinical and radiographic evidence of symptomatic apical periodontitis. It was determined based on the clinical symptoms severe preoperative pain (VAS > 60) and severe percussion pain (VAS > 60), confirmed by positive response to hot and cold tests. Thermal pulp testing was performed by the author, and radiographic interpretation was verified by one certified oral surgeon.
Fifty-four of 65 patients (29 women and 25 men), 18 to 60 years of age with 54 eligible teeth consented to participate in the study. The study design is shown in Figure 1. The patients were randomly divided into three groups using a web program. The patient number and group number were recorded. Informed consent was obtained from each patient, and the possible discomforts and risks were fully explained.
A total of 54 patients were divided into three groups (n =18) according to the type of preoperative drug administrated, as follows: Group A: ketorolac 10mg (Siegfried Rhein S.A. de C.V, Mexico,DF), Group B: Diclofenac Na 50mg (Voltaren, Novartis Mexico), and Group C: A placebo (capsule filled with sugar).
A registered pharmacist compounded identical-appearing capsules of the ketorolac, Diclofenac Na, and the placebo (opaque yellow size “0” capsules). All medications were placed in identical bottles so that they were indistinguishable to the investigator.
The administration of drugs and root canal treatment were performed by two different researchers. One researcher knew the allocation and the drug type in the capsules, but the operator and the patient did not know which drug type was administered.
Patient selection was based on the following criteria:
- The aims and requirements of the study were freely accepted.
- Treatment was limited to patients in good health.
- Patients with symptomatic or asymptomatic teeth with vital pulps and apical periodontitis.
- A positive response to hot and cold pulp sensitivity tests.
- Presence of sufficient coronal tooth structure for rubber dam isolation.
- No prior endodontic treatment on the involved tooth.
- No analgesics or antibiotics were used 5 days before the clinical procedures began.
Exclusion criteria included the following:
- Patients who did not meet inclusion requirements.
- Patients who did not provide authorization for participation.
- Patients who were younger than 16 years old.
- Patients who were pregnant.
- Patients who were diabetic.
- Patients with a positive history of antibiotic use within the past month.
- Patients whose tooth had been previously accessed or endodontically treated.
- Teeth with root resorption.
- Immature/open apex, or a root canal in which patency of the apical foramen could not be established were all excluded from the study. Teeth with periodontal pockets deeper than 4 mm, or the presence of a periapical radiolucency more than 3 cm diameter also were excluded from the study. Also excluded were patients whose affected tooth and related work had any of the following issues: curved roots, problems in determining working length, broken files, over-instrumentation, and over or incomplete filling.
Once eligibility was confirmed, the study was explained to the patient by the authors, and the patient was invited to participate. After explaining the clinical procedures and risks and clarifying all questions raised, each patient signed a written informed consent form and was randomly assigned to either of the three groups by using a block of random numbers generated by one of the investigators.
A medical history was obtained and a clinical examination performed. Of all teeth, 11 were asymptomatic and 43 symptomatic with a diagnosis of pulpitis determined by hot and cold sensitivity tests. Radiographically, all teeth showed a small and irregular radiolucency at the tooth apex (Schick Technologies; Long Island City, New York). The diagnostic findings were checked by comparing the tooth’s response against that of an adjacent tooth with a vital pulp. Periodontal probing revealed no increased probing depth (> 3 mm) around any of the teeth. The author performed all the clinical procedures.
All treatment sessions were approximately 50 minutes in length to allow for acceptable time for completion of treatment in one or two visits. The author performed all the clinical procedures. The standard procedure for the three groups included local anesthesia with 2% lidocaine with 1:100,000 epinephrine (Septodont; Saint-Maur des Fossés, France) and rubber dam isolation. The tooth was disinfected with 5.25% NaOCl (Ultra bleach; Bentonville, Arkansas).
Carious dentin was completely removed and endodontic access cavities prepared with sterile high-speed carbide burs No. 331 (SS White; Lakewood, New Jersey) and Zekrya Endo burs (Dentsply-Maillefer; Ballaigues, Switzerland). After gaining access, the canals were explored with No. 06, No. 08, and No. 10 K-type hand files (Flex-R® files; Moyco/Union Broach, York, Pennsylvania) according to the initial diameter of the foramen, its degree of flattening, and its canal curvature using a watch-winding motion.
Working length (WL) was established by introducing a No. 10 K-file up to the apical foramen as determined by a Root ZX (J Morita; Irvine, California), and then by withdrawing the file and subtracting 0.5 mm from the length, which was measured with the aid of an endodontic ruler. The WL was confirmed radiographically (Schick Technologies; Clark Dental UK).
The root canals were negotiated and enlarged with hand instruments (Flex-R files; Moyco/Union Broach, York Pennsylvania) until reaching an ISO size No. 20 at working length. The coronal portions of the root canals were flared with sizes 2-3 Gates- Glidden burs (Dentsply Maillefer). Irrigation with 2mL 2.5% sodium hypochlorite (NaOCl) was performed using a 24-G needle (Max-i-Probe®; Dentsply Sirona) during access and a 31-G NaviTip® needle (Ultradent Products Inc., South Jordan, Utah) when reaching the WL after each file insertion.
Reciprocating files (VDW, Munich Germany) were used to complete root canal preparation. EDTA (Roth International Ltd, Chicago, Ilinois) served as a lubricant. All reciprocating files were driven by an electric micro motor with limited torque (VDW.Silver Reciproc® motor; QED UK). R25 files (25.08) were used in narrow and curved canals, and R40 files (40.06) were used in large canals. Three in-and-out (pecking) motions were applied with stroke lengths not exceeding 3 mm in the cervical, middle, and apical thirds until attaining the established WL. All the files were used in only one tooth (single use) and then discarded. Patency of the apical foramen was maintained during all the techniques by introducing a No. 10 K-type file at WL. The preparations for all the groups were finished using a No. 45 file for narrow or curved canals and a No. 60 file for wide canals.
After completion of instrumentation, all root canals were irrigated with 2.5 mL 17% EDTA acid (Roth International) for 30 seconds followed by a final irrigation with 5.0 mL 5.25% NaOCl using the EndoVac® irrigation system (Discus Dental; Culver City, California). The root canals were dried with sterile paper points and obturated at the same appointment using lateral condensation of gutta percha and Sealapex® sealer (SybronEndo). Access cavities of anterior teeth were etched and restored with Fuji IX (GC UK). For posterior teeth, a buildup restoration was placed using the same etching technique and Fuji IX.
After completing the endodontic treatment procedure, all patients were given postoperative instructions to take analgesics (400 mg ibuprofen) in the event of pain at a dosage of one tablet every 6 hours.
The level of discomfort was rated as follows: no pain; mild pain, which was recognizable but not discomforting; moderate pain, which was discomforting but bearable (analgesics, if used, were effective in relieving pain); flare-up, which was difficult to bear (analgesics, if used, were ineffective in relieving pain). Cases with severe postoperative pain and/or the occurrence of swelling were classified as flare-ups and treated accordingly (Table 2). After completion of RCT, patients were instructed to return to their referring dentist for definitive restoration as soon as possible.
Patients were contacted by telephone by the clinical assistant after 24 hours, 48 hours, 72 hours, and 7 days and asked to provide the following information: their perceived pain rating and whether they had taken the analgesic medication prescribed and, if so, the quantity of tablets and the number of days required to control the pain. All the patients were instructed to contact the clinic or the dentist in charge of their treatment if the analgesic medication failed to provide pain relief or in the event of any other type of emergency.
The Kruskal-Wallis nonparametric test was applied to compare the incidence of postoperative pain. The level of significance adopted was 5% (p = 0.05). The final scale was as follows: None: 0-6.0, Faint: >6.0-17.0, Weak: >17.0-27.0, Mild: >27.0-42.3, Moderate: >42.3-60.3, Strong: >60.3-74.7, Intense: >74.7-90.6, and Maximum: >90.6 – 100.
A summary of the study can be seen in the Consort diagram. There were no statistically significant differences among the groups in terms of demographic data (Table 1) or pulp and periapical status (Table 2) (P >.05). Ketorolac and diclofenac Na showed clinically significant relief in pain for the next 3 days compared with the placebo group. In addition, no significant differences were demonstrated between ketorolac and diclofenac Na (Table 3). Similarly, there were no significant differences among the groups in terms of preoperative pain levels and percussion pain levels, but there was a difference in postoperative pain in placebo group.
Results from this study indicated that preoperative pain with the diagnoses of irreversible pulpitis with apical periodontitis were the most common for respondents to choose analgesics to relieve their patients’ pain. A total of seven patients needed analgesics postoperatively: five of these were in the placebo group, one in the ketorolac/tramadol group, and one in the diclofenac Na group. Table 3 shows lower pain levels in all groups.
In the present study, two patients experienced a flare-up. Two cases of flare-up were from the placebo group. Both required an intra-appointment visit. The flare-up from the patient in the placebo group showed no signs of swelling, but caused extreme pain. Upon opening the tooth, inflammatory drainage was established.
The purpose of this study was to evaluate the effect of preoperative administration of single-dose ketorolac, non-steroidal anti-inflammatory drug and placebo on postoperative pain in teeth with irreversible pulpitis and apical periodontitis. Practice background was significant for analgesic preferences relating to severe pain with an endodontic diagnosis of irreversible pulpitis with acute periradicular periodontitis (Gatewood, Himel, and Dorn, 1990).27 Our findings agree with Nusstein (Nusstein and Beck, 2003)28 relating to prescribe analgesic in teeth with irreversible pulpitis and symptomatic apical periodontitis.
Many local and systemic factors such as age, gender, general health, group of teeth, pulp and periapical status, and occlusal contacts, among others, may interact and modulate the occurrence of pain of endodontic origin (Hargreaves, Cohen, and Berman, 2011).29
Knowing those factors as predictors may contribute to defining preventive oral health strategies to manage this undesirable condition, minimizing pain incidence and/or intensity, and reducing patient suffering at the individual and population levels. Additionally, clinicians may use this information to advise patients about pain outcomes related to RCT (Law, Nixdorf, and Aguirre, 2015).30
The results of the present study indicated that some clinicians were more likely to choose medication before and after endodontic treatment to manage this painful clinical scenario, whereas other educators and residents were much more likely to prescribe combination drugs in addition to instrumentation (Litkowski, et al., 2005).31
Prescribing a drug before start root canal in patients with irreversible pulpitis will reduce postoperative pain or sensitivity. The results from this present study are consistent with the findings of Law (Law, Nixdorf, and Aguirre, 2015)30 that to avoid severe postoperative pain in endodontic therapy, preemptive analgesia strategies before initiation of treatment are necessary and with Krasner and Jackson (Krasner and Jackson, 1986)32 who noted from their study that although pulpectomy eliminates endodontic pain, postoperative pain and discomfort.
Two previous investigations have reported that the prophylactic use of analgesics at the end of the treatment visit had a positive influence on postoperative pain felt by the patients (Morse, Esposito, and Furst, 1990; Mehrvarzfar, 2012).11,33 Therefore, in the present study, all patients were instructed to take the first dose of the drug 15 minutes before start the treatment visit.
Considering the multifactorial nature of preoperative pain and postoperative pain, prevention and treatment strategies should depend on the identification and management of key predisposing factors (Siqueira, et al., 2002; Ng, Mann, and Gulabivala, 2011).4,34
Pain intensity is therefore influenced by various factors, including environmental, previous experience, mental health, and attitude making it a challenge to measure. Numerous scales have been used for pain intensity evaluation. Of these, the numerical rating scale (NRS), is a scale with end points of the extremes of no pain and as bad as it could be or the worst pain. There is also the visual rating scale (VRS), which is made up of a list of descriptors that represent the level of pain intensity. It is subjective, and its association with disease may be indirect; however, it is a personal qualitative judgment of patients’ perception of pain strength (Pasqualini, 2012).8
In this study, the visual analogue scale (VAS) was used that is a 10 cm line arrangement that relates to verbal parameters. Its value as a measurement is well-documented and another form to evaluate the response of the patients’ pain to the analgesics.
To show the real amount/perception of postoperative pain felt by patients, it appears to be reasonable for researchers to provide two evaluation forms: one to include the conventional VAS and another form to evaluate the response of the patients’ pain to the analgesics (Lund, et al., 2005; Lara-Munoz, et al., 2004).35,36
Additionally, visual analogue scales (VAS) and numeric rating scales (NRS) for assessment of pain intensity agree well, are equally sensitive in assessing acute pain, and are superior to a four-point verbal categorical rating scale (Breivik, et al., 2008).37 Hence, in the present study, patients were given one such form, and the results showed that some patients reported severe pain that was unbearable and not interfered with the patient’s daily activities with no significant difference between the groups A and B.
Our findings agree with Wells (Wells, et al., 2011)38 that reported the presenting initial moderate pain level is representative of emergency patients with symptomatic teeth, a pulpal diagnosis of necrosis, and a periapical radiolucency. Postoperative pain or sensitivity is often used to assess the quality of analgesics because of its consistency and intensity.
Preoperative examination, interpretation of symptoms, and diagnosis are crucial factors in long-term success of endodontic therapy. No controversies exist regarding the fact that teeth diagnosed with irreversible pulpitis should be treated in one session, if no technical complications arise (Paredes-Vieyra and Enriquez, 2012).39 However, in cases of pulp necrosis with or without periradicular periodontitis, the literature is more controversial. Although preoperative administration of analgesics has been found to be effective in reducing postoperative pain (Hargreaves, Cohen, and Berman, 2011; Law, Nixdorf, and Aguirre, 2015),29,30 there have been various studies related to the effect of the preoperative administration of antihistamines on postoperative pain.
Wells (38) found that there were decreases in postoperative pain levels with the preoperative administration use of ibuprofen, a finding in harmony with ours. The decreased pain levels in the analgesic group can be explained by the ability of analgesics to eliminate pain resulting in blocking of nociceptive sensory nerve fibers (Dale, et al., 1918; Hargreaves, et al., 1994).20,29
An interesting finding in the present study was that while the preoperative administration of ketorolac resulted in less pain than that of a diclofenac Na, there was no significant difference between ketorolac and diclofenac Na administration. This finding suggests that the preoperative administration of ketorolac as a single dose before the treatment is beneficial in reducing postoperative pain. Pain of endodontic origin depends on the multidimensional interrelationship between host, pulp, and periapical tissues, and the nature of endodontic procedures. The measurement of pain intensity is a reasonable way to evaluate treatment efficacy.
A single dose of ketorolac was as effective or as safe as NSAID for the relief of pain after operations on postoperative pain in teeth with symptomatic apical periodontitis.
- Sessle BJ. Recent developments in pain research: central mechanisms of orofacial pain and its control. J Endod. 1986;12(10):435-444.
- Cunningham CJ, Mullaney TP. Pain control in endodontics. Dent Clin North Am. 1992;36:(2)393-408.
- Arias A, de la Macorra JC, Hidalgo JJ, Azabal M. Predictive models of pain following root canal treatment:(0)a prospective clinical study. Int Endod J. 2013;46:(8)784-793.
- Siqueira JF Jr, Rôças IN, Favieri A, et al. Incidence of postoperative pain after intracanal procedures based on an antimicrobial strategy. J Endod. 2002;28:(6)457-460.
- Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: a systematic review. J Endod. 2011;37:(4)429-438.
- Sathorn C, Parashos P, Messer H. The prevalence of postoperative pain and flare-up in single- and multiple-visit endodontic treatment: a systematic review. Int Endod J. 2008;41:(2)91-99.
- Parirokh M, Yosefi MH, Nakhaee N, Manochehrifar H, Abbott PV, Reza Forghani F. Effect of bupivacaine on postoperative pain for inferior alveolar nerve block anesthesia after single-visit root canal treatment in teeth with irreversible pulpitis. J Endod. 2012;38:(8)1035-1039.
- Pasqualini D, Mollo L, Scotti N, et al. Postoperative pain after manual and mechanical glide path: a randomized clinical trial. J Endod. 2012;38:(1)32-36.
- Parirokh M, Rekabi AR, Ashouri R, Nakhaee N, Abbott PV, Gorjestani H. Effect of occlusal reduction on postoperative pain in teeth with irreversible pulpitis and mild tenderness to percussion. J Endod. 2013;39:(1)1-5.
- Rosenberg PA, Babick PJ, Schertzer L, Leung A. The effect of occlusal reduction on pain after endodontic instrumentation. J Endod. 1998;24:(7)492-496.
- Morse DR, Esposito JV, Furst ML. Comparison of prophylactic and on-demand diflunisal for pain management of patients having one-visit endodontic therapy. Oral Surg Oral Med Oral Pathol. 1990;69(6):729-736.
- Attar S, Bowles WR, Baisden MK, Hodges JS, McClanahan SB. Evaluation of pretreatment analgesia and endodontic treatment for postoperative endodontic pain. J Endod. 2008;34:(6)652-655.
- Menhinick KA, Gutmann JL, Regan JD. The efficacy of pain control following nonsurgical root canal treatment using ibuprofen or a combination of ibuprofen and acetaminophen in a randomized, double-blind, placebo-controlled study. Int Endod J. 2004;37(8):531-541.
- Ryan JL, Jureidini B, Hodges JS, Baisden M, Swift JQ, Bowles WR. Gender differences in analgesia for endodontic pain. J Endod. 2008;34:(5)552-556.
- Morse DR, Furst ML, Koren LZ, Bolanos OR, Esposito JV, Yesilsoy C. Comparison of diflunisal and an aspirin-codeine combination in the management of patients having one-visit endodontic therapy. Clin Ther. 1987;9:(5)500-511.
- Sadeghein A, Shahidi N, Dehpour AR. A comparison of ketorolac tromethamine and acetaminophen codeine in the management of acute apical periodontitis. J Endod. 1999;25:(4):257-259.
- Pochapski MT, Santos FA, de Andrade ED, Sydney GB. Effect of pretreatment dexamethasone on postendodontic pain. Oral Surg Oral Med Oral Pathol. 2009;108(5):790-795.
- Bender IB. Pulpal pain diagnosis—a review. J Endod. 2000;26:(3)175-179.
- Oliveira SM, Drewes CC, Silva CR, et al. Involvement of mast cells in a mouse model of postoperative pain. Eur J Pharm. 2011;672(1-3):88-95.
- Dale HH, Richards AN. The vasodilator action of histamine and of some other substances. J Physiol. 1918; 52(2-3):110-165.
- Hargreaves KM, Swift JQ, Roszkowski MT, Bowles W, Garry MG, Jackson DL. Pharmacology of peripheral neuropeptide and inflammatory mediator release. Oral Surg Oral Med Oral Pathol. 1994;78:(4)503-510.
- Levin L, Amit A, Ashkenazi M. Post-operative pain and use of analgesic agents following various dental procedures. Am J Dent. 2006;19:(4)245–247.
- Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43:(13)879-923.
- Mishra H, Khan FA. A double-blind, placebo-controlled randomized comparison of pre- and postoperative administration of ketorolac and tramadol for dental extraction pain. J Anaesthesiol Clin Pharmacol. 2012;28:(2)221-225.
- Desjardins PJ, Fricke JR, Mardirossian G, Seng GF, Beirne OR. Bromfenac, a nonopioid analgesic, compared with tramadol and placebo for the management of postoperative pain. Clin Drug Investig. 1998;15:(3)177-185.
- Shah AV, Arun-Kumar KV, Kumar-Rai K, Rajesh-Kumar BP. Comparative evaluation of pre-emptive analgesic efficacy of intramuscular ketorolac versus tramadol following third molar surgery. J Maxillofac Oral Surg. 2013;12:(2)197-202.
- Gatewood RS, Himel VT, Dorn SO. Treatment of the endodontic emergency: a decade later. J Endod. 1990;16:(6)284-291.
- Nusstein JM, Beck M. Comparison of preoperative pain and medication use in emergency patients presenting with irreversible pulpitis or teeth with necrotic pulps. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:(2)207-214.
- Hargreaves KM, Cohen S, Berman LH. Cohen’s Pathways of the Pulp. 10th ed. St. Louis, MO: Mosby Elsevier; 2011.
- Law AS, Nixdorf DR, Aguirre AM, et al. Predicting severe pain after root canal therapy in the National Dental PBRN. J Dent Res. 2015;94(suppl 3):37S-43S.
- Litkowski LJ, Christensen SE, Adamson DN, Van Dyke T, Han SH, Newman KB. Analgesic efficacy and tolerability of oxycodone 5 mg/Ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model. Clin Ther. 2005;27(4):418-429.
- Krasner P, Jackson E. Management of posttreatment endodontic pain with oral dexamethasone: a double-blind study. Oral Surg Oral Med Oral Pathol. 1986;62:(2)187-190.
- Mehrvarzfar P, Abbott PV, Saghiri MA, et al. Effects of three oral analgesics on postoperative pain following root canal preparation: a controlled clinical trial. Int Endod J. 2012;45:(1)76-82.
- Ng YL, Mann V, Gulabivala K. A prospective study of the factors affecting outcomes of nonsurgical root canal treatment: part 1: periapical health. Int Endod J. 2011;44:(7)583-609
- Lund I, Lundeberg T, Sandberg L, Budh CN, Kowalski J, Svensson E. Lack of interchangeability between visual analogue and verbal rating pain scales: a cross sectional description of pain etiology groups. BMC Med Res Methodol. 2005;5:31
- Lara-Munoz C, De Leon SP, Feinstein AR, Puente A, Wells CK. Comparison of three rating scales for measuring subjective phenomena in clinical research: I. Use of experimentally controlled auditory stimuli. Arch Med Res. 2004;35:(1)43-48.
- Breivik H, Borchgrevink PC, Allen SM, et al. Assessment of pain. Br J Anaesth. 2008;101(1):17-24.
- Wells LK, Drum M, Nusstein J, et al. Efficacy of ibuprofen and ibuprofen/acetaminophen on postoperative pain in symptomatic patients with a pulpal diagnosis of necrosis. J Endod. 2011;37(12):1608-1612.
- Paredes-Vieyra J, Enriquez FJ. Success rate of single- versus two-visit root canal treatment of teeth with apical periodontitis: a randomized controlled trial. J Endod. 2012;38:(9)1164-1169.