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Effects of analgesics on orthodontic pain

Shreena Patel,a Susan P. McGorray,b Robert Yezierski,c Roger Fillingim,d Henrietta Logan,e and Timothy T. Wheelerf Jacksonville and Gainesville, Fla Introduction: Our objective was too assess the effectiveness of 3 analgesics (ibuprofen, naproxen sodium, and acetaminophen) and a placebo administered before and after the placement of separators in reducing the severity of postseparator placement pain. We also examined the impact of treatment on chewing efciency at 24 hours after separator placement. Methods: Twenty-four subjects participated in the study. Each subject received 3 of 4 treatments: ibuprofen, naproxen sodium, acetaminophen, or placebo in random order at monthly intervals. The dosing times were 1 hour before separator placement and 3 and 7 hours after separator placement. Before placement, the subjects completed a masticatory efciency test and a visual analog scale (VAS) for expected pain and pain experienced. A VAS pain diary was kept for 24 hours. Subjects returned to the clinic after 1 week for separator removal. Results: VAS pain summary scores after separator placement were signicantly affected by the administration of ibuprofen (P 5 0.0298) and the time after separator placement (P \0.0001). Administering ibuprofen before and after separator placement signicantly reduced pain compared with the placebo. The analgesic effects diminished by day 2, resulting in peak pain levels and decreased chewing efciency. The expected pain after separator placement also played a role in experienced pain; subjects expecting more pain experienced more pain. Conclusions: Ibuprofen was superior to the placebo in relieving postseparator pain as measured by the VAS pain summary scores, whereas acetaminophen and naproxen sodium did not signicantly differ from the placebo. (Am J Orthod Dentofacial Orthop 2011;139:e53-e58)

ain is a widespread concern in dentistry, including the specialty of orthodontics. Between 90% and 95% of patients undergoing orthodontic treatment report pain with appliances.1-3 A survey of patients attitudes toward orthodontic treatment indicated that pain is the most discouraging aspect of treatment and the primary reason for wanting to discontinue care.4 Pain after orthodontic treatment is usually felt within a few hours, reaching maximum levels 24 hours after treatment. After 1 week, the level of discomfort usually decreases.5 There is evidence that about 25% to 45%
a

Private practice, Jacksonville, Fla. Research assistant professor, Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville. c Professor, Department of Orthodontics, College of Dentistry, University of Florida, Gainesville. d Professor, Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville. e Professor, Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville. f Professor, Department of Orthodontics, College of Dentistry, University of Florida, Gainesville. The authors report no commercial, proprietary, or nancial interest in the products or companies described in this article. Reprint requests to: Susan P. McGorray, Box 100177, Department of Epidemiology and Health Policy Research, University of Florida College of Medicine, Gainesville, FL 32610-0177; e-mail, spmcg@biostat.u.edu. Submitted, February 2010; revised and accepted, July 2010. 0889-5406/$36.00 Copyright 2011 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2010.07.017
b

of patients still experience pain after 7 days of appliances.3,6 Differences in treatment, whether separators, appliances, or archwires, might explain the conicting results among studies. With such a high incidence of discomfort, pain control and management are an obvious interest for clinicians and patients alike. Nonsteroidal anti-inammatory drugs (NSAIDs) include ibuprofen and naproxen sodium and are often used for their analgesic, anti-inammatory, and antipyretic effects. Because of the gastrointestinal side effects associated with NSAIDs, acetaminophen might be recommended.7 Acetaminophen is classied as a nonopiod analgesic with analgesic and antipyretic properties.8 Acetaminophen does not have the anti-inammatory component that is characteristic of NSAIDs. Ngan et al5 were the rst to evaluate analgesics to control discomfort associated with orthodontic treatment. They administered 400 mg of ibuprofen or 650 mg of aspirin immediately after separator or initial archwire placement. Steen Law et al9 took this a step further and instructed patients to also take a dose of 400 mg of ibuprofen 1 hour before separator placement. Both studies found pain reduction with ibuprofen. Minor et al10 also supported the administration of ibuprofen before and after separator placement to decrease the pain experienced at 6 hours, bedtime, and the morning after separator placement. Polat and Karaman11 studied several analgesics. They found that naproxen sodium and aspirin
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administered before and after separator placement more effectively reduced pain compared with ibuprofen, urbiprofen, and a placebo. More recently, Bird et al12 found no signicant differences in pain over a 24-hour period after a single dose of acetaminophen or ibuprofen administered 1 hour before separator placement. Based on the literature, it is apparent that there is no accepted regimen for treating orthodontic pain. The objective of this prospective, randomized, double-blind, placebo-controlled crossover clinical trial was to compare the effectiveness of 3 analgesic drugs (ibuprofen, naproxen sodium, and acetaminophen) administered to reduce the incidence and severity of pain after the placement of separators. We also evaluated the effect of treatment assignment on chewing efciency at 24 hours after separator placement.
MATERIAL AND METHODS

Before the rst dosing (T0), the following measurements were completed by all subjects. 1. Expectation of pain after separator placement using a 100-mm visual analog scale (VAS) with anchors of no pain and worst pain imaginable.13 Modied mastication performance index, for which the subjects chewed 1 bagged almond 5 times on the right side of the mouth without swallowing.14 This was repeated on the left side of the mouth with another bagged almond. VAS pain ratings as a consequence of chewing the almond were recorded.

2.

Twenty-four subjects participated in this study at the University of Florida Orthodontic Clinic. Each participant met these inclusion criteria: (1) between 18 and 30 years of age; (2) not pregnant; (3) second premolars, rst molars, and second molars in contact, allowing the placement of 2 separators in each of the 4 quadrants; (4) not taking pain medications; (5) no contraindications to the drugs under study or almonds, (6) no need for antibiotic prophylaxis before dental treatment; and (7) informed consent for participation in the study. The study was approved by the University of Florida Institutional Review Board for the Protection of Human Subjects. Each subject was randomized to receive 3 of 4 treatments (ibuprofen, naproxen sodium, acetaminophen, or placebo) over 3 months. The dose and timing for each treatment varied slightly because they were based on over-the-counter directions for each medication. The dosing times for each treatment were 1 hour (D1) before separator placement, and 3 (D2) and 7 (D3) hours after separator placement. The separators were removed after 1 week. One and 2 months from the start of participation, the subjects returned to the clinic and received a second treatment. By the end of the 3 months (periods), each subject had received 3 of the 4 treatments. The dosing amounts for each drug were 400 mg of ibuprofen at D1, D2, and D3; 500 mg of naproxen sodium at D1, placebo at D2, and 250 mg of naproxen sodium at D3; 650 mg of acetaminophen at D1, D2, and D3; and placebo at D1, D2, and D3. The Investigational Drug Service at Shands Hospital, Gainesville, Fla, encapsulated and dispensed the tablets; consequently, the researchers were blinded to the treatment group assignment.

Two separators (P/N 640-0080, Ormco, Glendora, Calif) were placed in each quadrant, mesially and distally to the rst molar. The method of placement was under the contact for all subjects. Pain at separator placement was recorded with the VAS. Over the next 24 hours, the subjects recorded discomfort when biting, chewing, tting front teeth together, and tting back teeth together in a VAS pain diary, similar to that used in other studies.5,9,15,16 VAS assessments were recorded at 2 hours after separator placement (T1), 6 hours after separator placement (T2), bedtime (T3), upon awakening (T4), and 24 hours after separator placement (T5). The remaining 2 doses were self-administered by the subject at D2 and D3. At T5, the subject completed the masticatory efciency test with the VAS. The completed pain diary and the chewed bagged almonds were brought to the next appointment. To analyze the chewed almonds, the whole sample was weighed and sieved through a #10 mesh, and the separated sample was weighed. The chewing efciency was the percentage of the original sample that passed through the sieve.
Statistical analysis

Descriptive statistics were calculated for pain scores and masticatory chewing efciency at each time point for each treatment group. Linear mixed models were used to examine VAS pain scores over time and chewing efciency.17 The initial model for the VAS pain summary score (sum of pain ratings for biting, right and left; chewing, right and left; tting back teeth together; and tting front teeth together) included the following variables: treatment, period (month 1, 2, or 3), prior treatment (to assess carryover effects), order, time point, and treatment by time-point interaction. The interaction allowed the pain response pattern to vary over time depending on the treatment group. This model was used to evaluate differences in treatment effects at specic time points. A reduced model was examined, excluding period, prior treatment, or treatment by time-point interaction, if they did not achieve statistical signicance in

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Ibuprofen Naproxen Acetaminophen Placebo

VAS pain summary score

10

20

30

2 hours

6 hours

bedtime time point

awakening

24 hours

Fig. Mean and standard error bars for VAS pain summary scores, by treatment assignment and time point.

the initial model. The initial model for 24-hour chewing efciency included treatment, baseline chewing efciency, period, and prior treatment. For signicant main effects, contrasts were used to identify the specic groups that differred. For both outcomes, the impact of adding additional covariates (expected pain and sex) to the initial model was also examined. For all analyses, a P value less than 0.05 was considered statistically signicant. SAS software (version 9.1, SAS Institute, Cary, NC) was used for the statistical analyses.
RESULTS

The sample consisted of 11 women (46%) and 13 men (54%); 75% were white, 13% Asian, 8% other, and 4% Hispanic. Their ages ranged from 19 to 30 years, with a mean age of 26.4 years (SD, 2.5). Mean VAS pain summary scores by treatment groups and time points are displayed in the Figure. Our initial mixed model did not indicate signicant effects due to period (P 5 0.85), prior treatment (P 5 0.84), order (P 5 0.91), or time point by treatment interaction (P 5 0.68). The reduced model detected signicant effects from treatment

assignment (P 5 0.0298) and time point (P \0.0001). Parameter estimates for this model are listed in Table I. Contrasts were used to identify treatments that differed: ibuprofen vs placebo (P 5 0.0034), and a borderline difference was seen between naproxen and the placebo (P 5 0.0563). Contrasts also indicated that all time periods differed from each other (P \0.0001) except for the T2 and T3 time points (P 5 0.41). The initial model for the VAS pain summary score was evaluated to further identify treatment differences at specic time points. Subjects who took ibuprofen reported signicantly less pain than those who took the placebo at 2 and 6 hours after separator placement, as well as at bedtime and awakening. Acetaminophen and naproxen sodium did not show signicant differences compared with the placebo at any time point. By 24 hours postplacement, which was 17 hours after the last medication dose, pain levels returned to those of the placebo for all subjects (P 5 0.27). We next examined the impact of additional covariates: sex and expected pain. No signicant effect in the VAS pain summary score due to sex was found (P 5 0.37).

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Table I. Estimates of xed effects from mixed model analysis, with the dependent variable the VAS pain summary score
Parameter Intercept Treatment Ibuprofen Naproxen sodium Acetaminophen Placebo Time point 2 hours 6 hours Bedtime Awakening 24 hours Estimate (SE) 30.70 (2.70) 7.89 (2.59) 5.04 (2.50) 3.67 (2.50) (reference) 16,46 (1.42) 11.64 (1.32) 10.90 (1.16) 5.74 (0.89) (reference) P value \0.0001 0.0035 0.0563 0.1614

Table II. Estimates of the xed effects from the mixed analysis for model including expected pain and expected pain by time interaction, with dependent variable the VAS pain summary score
Parameter Intercept Treatment Ibuprofen Naproxen sodium Acetaminophen Placebo Time point 2 hours 6 hours Bedtime Awakening 24 hours Expected pain Expected pain 3 time interaction Expected pain 3 2 hours Expected pain 3 6 hours Expected pain 3 bedtime Expected pain 3 awakening Expected pain 3 24 hours Estimate (SE) 21.45 (3.22) 6.54 (2.46) 3.45 (2.47) 1.75 (2.49) (reference) 9.43 (2.27) 5.92 (2.12) 7.25 (1.88) 6.64 (1.45) (reference) 2.27 (0.48) 1.99 (0.52) 1.62 (0.48) 1.03 (0.43) 0.26 (0.33) (reference) P value \0.0001 0.0103 0.1679 0.4853

\0.0001 \0.0001 \0.0001 \0.0001

\0.0001 0.0056 0.0001 \0.0001 \0.0001 0.0001 0.0009 0.0157 0.4353

However, expected pain had a signicant effect on the VAS pain summary score, and its impact varied over time. The coefcient estimates for this model are presented in Table II. Considering both the impact of expected pain and the expected pain by time point interaction, we saw that expected pain had the greatest impact on later pain scores, at T4 and T5. By this time, pain medication would have worn off, and the pain that the subjects felt was consistent with their expectations. For example, from the model, with all other factors equal, we could compare the predicted VAS pain summary score for a subject with an expected pain rating of 1.0 with that of a subject with an expected pain rating of 7. The subject with the higher expected pain rating (7) would have predicted VAS pain summary scores 1.7 points higher at 2 hours and 13.6 points higher at 24 hours, than the subject with the expected pain rating of 1. We analyzed the pain score further to examine individual components (chewing, biting, tting front teeth together, and tting back teeth together). The results were similar to the overall model for chewing, biting, and tting back teeth together, with signicant day and treatment effects detected. However, signicant treatment effects were not seen for tting the front teeth together. For all treatment groups, chewing efciency decreased markedly from T0 to T5. Considering chewing efciency at T5, the mixed model analysis indicated no signicant differences from treatment assignment (P 5 0.36), prior medication (P 5 0.80), or period (P 5 0.88). However, the efciency at T0 was a signicant predictor of the performance at T5 (P 5 0.0131). Sex and expected pain rating did not affect chewing efciency at T5. Mean chewing efciency at T0 was 46.6% (SD, 14.1%); this dropped to 17.5% (SD, 14.6%) at T5.

DISCUSSION

In this study, pain after separator placement was signicantly related to the treatment drug and the time after placement. Subjects who received ibuprofen reported signicantly less pain than those who received the placebo. These results are consistent with previous studies in support of ibuprofen before and after treatment.9,10,16,18 Bird et al,12 on the other hand, found no signicant differences in postseparator pain with either acetaminophen or ibuprofen. In contrast to our study, the drugs were administered only 1 hour before separator placement, with no follow-up doses. Polat and Karaman11 studied several analgesics and recommended acetaminophen over naproxen sodium or aspirin. Although subjects who took naproxen sodium and aspirin felt almost no pain at 24 hours, the acetaminophen group showed similar pain scores, without the side effects associated with NSAIDs. Compared with the placebo, in this study, we found signicant differences only for ibuprofen, not naproxen sodium or acetaminophen. There were differences between this study and that of Polat and Karaman11 in regard to the drugs administered, dosing, and time; the subjects ages; and the stimulus to induce pain. Whereas 1100 mg of naproxen sodium was administered in the study of Polat and Karaman, only 750 mg were used in our study. Our subjects were adults, and separators were used to induce pain. Subjects in the study

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by Polat and Karaman were adolescents, and initial archwires were placed to induce pain. The design of this study was well suited for studying pain relief. All previous studies on managing orthodontic pain with analgesics were parallel arm, in which each subject received only 1 treatment. In our study, nonorthodontic subjects were selected, and, with the incomplete block crossover design, all subjects received 3 of the 4 possible treatments. Because of the subjective nature of pain, within-subject assessment most likely provided more power than parallel-arm studies. Pain scores at the different time points all signicantly differed from each other, with the exception of T2 and T3. These results are comparable with those of Steen Law et al9 and Bernhardt et al,16 who found no differences in pain scores at 6 hours after treatment with ibuprofen. A recent study reported signicantly less pain at 6 hours, bedtime, and awakening, with no differences detected at 2 or 24 hours.10 Although in all of these studies 400 mg of ibuprofen was administered 1 hour before separator placement, they varied on the postseparator placement doses. For the T0 and T5 chewing efciencies, no signicant differences were seen among the treatment drugs. Signicant differences are not expected, since the T0 chewing efciency was before the administration of drugs. By T5, the analgesic effects had dissipated with the dosing regimen followed in the study. Expected pain was a signicant factor in predicting the pain experience. This agrees with other studies that reported a positive correlation between psychological factors and perceived pain.19,20 A longitudinal population-based study by Maggirias and Locker20 evaluated psychological factors and pain associated with dental treatment. Their results were based on 1422 adults who completed questionnaires. They found a strong relationship between perceived pain and psychological factors; pain was more often reported by patients with previous traumatic experiences, those who expected treatment to be painful, and those who were anxious about the treatment. In spite of the positive results reported in our study, there are concerns with the use NSAIDs to alleviate orthodontic pain. Orthodontic tooth movement requires remodeling of the periodontium, resulting in inammation, which leads to bone resorption.21 Inammatory mediators, such as prostaglandin E and interleukin-1 are released and interact with bone cells, promoting bone resorption.22 Because NSAIDs function by interfering with prostaglandin synthesis from arachidonic acid, it is reasonable to question whether administering these medications to relieve orthodontic pain will interfere with tooth movement. According to Prott and Fields,23

most pain medications do not reach high enough levels in the blood to inhibit tooth movement. Several studies have shown that the inhibition of prostaglandins by NSAIDs does prevent or delay orthodontic tooth movement.24-27 It is important to consider the length of time these medications are taken and the amounts administered. Short-term administration of NSAIDs will only temporarily affect prostaglandin levels; longterm use of these drugs should be avoided.5,26 Research showed that doses of 2400 to 3200 mg per day of ibuprofen are required to achieve antiinammatory effects over analgesic effects.7 The doses administered in this study did not reach antiinammatory levels.
CONCLUSIONS

Ibuprofen administered 1 hour before separator placement, and 3 and 7 hours after placement, reduced postseparator placement pain compared with a placebo. Acetaminophen and naproxen sodium did not show signicant differences compared with the placebo. The analgesic effects diminished by day 2, resulting in peak pain levels and decreased chewing efciency at this time. Additional drugs might be necessary to maintain pain relief. The expected pain also plays a role in experienced pain; subjects who expect more pain also report more pain.
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19. Firestone AR, Scheurer PA, Burgin WB. Patients anticipation of pain and pain-related side effects and their perception of pain as a result of orthodontic treatment with xed appliances. Eur J Orthod 1999;21:387-96. 20. Maggirias J, Locker D. Psychological factors and perceptions of pain associated with dental treatment. Community Dent Oral Epidemiol 2002;30:151-9. 21. Storey E. The nature of tooth movement. Am J Orthod Dentofacial Orthop 1973;63:292-314. 22. Grieve WG, Johnson GK, Moore RN, Reinhardt RA, DuBois LM. Prostaglandin E (PGE) and interleukin-1B (IL-B) levels in gingival crevicular uid during human orthodontic tooth movement. Am J Orthod Dentofacial Orthop 1994;105:369-74. 23. Proit WR, Fields HW. Contemporary orthodontics. 3rd ed. St Louis: Mosby; 1999. 24. Chumbley AB, Tuncay OC. The effect of indomethacin (an aspirinlike drug) on the rate of orthodontic tooth movement. Am J Orthod 1986;89:312-4. 25. Krykanides S, OBanion MK, Subtelny JD. Nonsteroidal antiinammatory drugs in orthodontic tooth movement: metalloproteinase activity and collagen synthesis by endothelial cells. Am J Orthod Dentofacial Orthop 2000;118:203-9. 26. Walker JB, Buring SM. NSAID impairment of orthodontic tooth movement. Ann Pharmacother 2001;35:113-5. 27. Tyrovola JB, Spyropoulos MN. Effects of drugs and systemic factors on orthodontic treatment. Quintessence Int 2001;32: 365-71.

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