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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 sever-
ity of postseparator placement pain. We also examined the impact of treatment on chewing efficiency 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 efficiency 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 significantly
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 significantly reduced pain compared with the
placebo. The analgesic effects diminished by day 2, resulting in peak pain levels and decreased chewing
efficiency. The expected pain after separator placement also played a role in experienced pain; subjects expect-
ing more pain experienced more pain. Conclusions: Ibuprofen was superior to the placebo in relieving postse-
parator pain as measured by the VAS pain summary scores, whereas acetaminophen and naproxen sodium did
not significantly differ from the placebo. (Am J Orthod Dentofacial Orthop 2011;139:e53-e58)

P
ain is a widespread concern in dentistry, including of patients still experience pain after 7 days of appli-
the specialty of orthodontics. Between 90% and ances.3,6 Differences in treatment, whether separators,
95% of patients undergoing orthodontic treatment appliances, or archwires, might explain the conflicting
report pain with appliances.1-3 A survey of patients’ results among studies. With such a high incidence of
attitudes toward orthodontic treatment indicated that discomfort, pain control and management are an
pain is the most discouraging aspect of treatment and obvious interest for clinicians and patients alike.
the primary reason for wanting to discontinue care.4 Nonsteroidal anti-inflammatory drugs (NSAIDs) in-
Pain after orthodontic treatment is usually felt within clude ibuprofen and naproxen sodium and are often
a few hours, reaching maximum levels 24 hours after used for their analgesic, anti-inflammatory, and antipy-
treatment. After 1 week, the level of discomfort usually retic effects. Because of the gastrointestinal side effects
decreases.5 There is evidence that about 25% to 45% associated with NSAIDs, acetaminophen might be rec-
ommended.7 Acetaminophen is classified as a nonopiod
analgesic with analgesic and antipyretic properties.8
a
Private practice, Jacksonville, Fla. Acetaminophen does not have the anti-inflammatory
b
Research assistant professor, Department of Epidemiology and Health Policy
Research, College of Medicine, University of Florida, Gainesville. component that is characteristic of NSAIDs.
c
Professor, Department of Orthodontics, College of Dentistry, University of Flor- Ngan et al5 were the first to evaluate analgesics to
ida, Gainesville. control discomfort associated with orthodontic treatment.
d
Professor, Department of Community Dentistry and Behavioral Science, College
of Dentistry, University of Florida, Gainesville. They administered 400 mg of ibuprofen or 650 mg of
e
Professor, Department of Community Dentistry and Behavioral Science, College aspirin immediately after separator or initial archwire
of Dentistry, University of Florida, Gainesville.
f
placement. Steen Law et al9 took this a step further and
Professor, Department of Orthodontics, College of Dentistry, University of Flor-
ida, Gainesville. instructed patients to also take a dose of 400 mg of ibu-
The authors report no commercial, proprietary, or financial interest in the profen 1 hour before separator placement. Both studies
products or companies described in this article. found pain reduction with ibuprofen. Minor et al10 also
Reprint requests to: Susan P. McGorray, Box 100177, Department of Epidemiology
and Health Policy Research, University of Florida College of Medicine, Gainesville, supported the administration of ibuprofen before and af-
FL 32610-0177; e-mail, [email protected]fl.edu. ter separator placement to decrease the pain experienced
Submitted, February 2010; revised and accepted, July 2010. at 6 hours, bedtime, and the morning after separator
0889-5406/$36.00
Copyright Ó 2011 by the American Association of Orthodontists. placement. Polat and Karaman11 studied several analge-
doi:10.1016/j.ajodo.2010.07.017 sics. They found that naproxen sodium and aspirin
e53
e54 Patel et al

administered before and after separator placement more Before the first dosing (T0), the following measure-
effectively reduced pain compared with ibuprofen, flurbi- ments were completed by all subjects.
profen, and a placebo. More recently, Bird et al12 found no
1. Expectation of pain after separator placement using
significant differences in pain over a 24-hour period after
a 100-mm visual analog scale (VAS) with anchors of
a single dose of acetaminophen or ibuprofen administered
“no pain” and “worst pain imaginable.”13
1 hour before separator placement.
2. Modified mastication performance index, for which
Based on the literature, it is apparent that there is no
the subjects chewed 1 bagged almond 5 times on the
accepted regimen for treating orthodontic pain. The ob-
right side of the mouth without swallowing.14 This
jective of this prospective, randomized, double-blind,
was repeated on the left side of the mouth with
placebo-controlled crossover clinical trial was to com-
another bagged almond. VAS pain ratings as a con-
pare the effectiveness of 3 analgesic drugs (ibuprofen,
sequence of chewing the almond were recorded.
naproxen sodium, and acetaminophen) administered
to reduce the incidence and severity of pain after the Two separators (P/N 640-0080, Ormco, Glendora,
placement of separators. We also evaluated the effect Calif) were placed in each quadrant, mesially and distally
of treatment assignment on chewing efficiency at 24 to the first molar. The method of placement was under
hours after separator placement. the contact for all subjects. Pain at separator placement
was recorded with the VAS. Over the next 24 hours, the
MATERIAL AND METHODS subjects recorded discomfort when biting, chewing, fit-
Twenty-four subjects participated in this study at the ting front teeth together, and fitting back teeth together
University of Florida Orthodontic Clinic. Each participant in a VAS pain diary, similar to that used in other stud-
met these inclusion criteria: (1) between 18 and 30 years ies.5,9,15,16 VAS assessments were recorded at 2 hours
of age; (2) not pregnant; (3) second premolars, first after separator placement (T1), 6 hours after separator
molars, and second molars in contact, allowing the placement (T2), bedtime (T3), upon awakening (T4),
placement of 2 separators in each of the 4 quadrants; and 24 hours after separator placement (T5). The
(4) not taking pain medications; (5) no contraindications remaining 2 doses were self-administered by the subject
to the drugs under study or almonds, (6) no need for at D2 and D3. At T5, the subject completed the mastica-
antibiotic prophylaxis before dental treatment; and (7) tory efficiency test with the VAS. The completed pain
informed consent for participation in the study. The diary and the chewed bagged almonds were brought
study was approved by the University of Florida Institu- to the next appointment.
tional Review Board for the Protection of Human To analyze the chewed almonds, the whole sample
Subjects. was weighed and sieved through a #10 mesh, and the
Each subject was randomized to receive 3 of 4 separated sample was weighed. The chewing efficiency
treatments (ibuprofen, naproxen sodium, acetamino- was the percentage of the original sample that passed
phen, or placebo) over 3 months. The dose and timing through the sieve.
for each treatment varied slightly because they were
based on over-the-counter directions for each medica- Statistical analysis
tion. The dosing times for each treatment were 1 hour Descriptive statistics were calculated for pain scores
(D1) before separator placement, and 3 (D2) and 7 (D3) and masticatory chewing efficiency at each time point
hours after separator placement. The separators were for each treatment group. Linear mixed models were
removed after 1 week. One and 2 months from the used to examine VAS pain scores over time and chewing
start of participation, the subjects returned to the clinic efficiency.17 The initial model for the VAS pain summary
and received a second treatment. By the end of the 3 score (sum of pain ratings for biting, right and left;
months (periods), each subject had received 3 of the chewing, right and left; fitting back teeth together;
4 treatments. and fitting front teeth together) included the following
The dosing amounts for each drug were 400 mg of variables: treatment, period (month 1, 2, or 3), prior
ibuprofen at D1, D2, and D3; 500 mg of naproxen treatment (to assess carryover effects), order, time point,
sodium at D1, placebo at D2, and 250 mg of naproxen and treatment by time-point interaction. The interaction
sodium at D3; 650 mg of acetaminophen at D1, D2, allowed the pain response pattern to vary over time de-
and D3; and placebo at D1, D2, and D3. The Investiga- pending on the treatment group. This model was used to
tional Drug Service at Shands Hospital, Gainesville, Fla, evaluate differences in treatment effects at specific time
encapsulated and dispensed the tablets; consequently, points. A reduced model was examined, excluding pe-
the researchers were blinded to the treatment group riod, prior treatment, or treatment by time-point inter-
assignment. action, if they did not achieve statistical significance in

January 2011  Vol 139  Issue 1 American Journal of Orthodontics and Dentofacial Orthopedics
Patel et al e55

Ibuprofen
Naproxen
30

Acetaminophen
Placebo
VAS pain summary score

20
10
0

2 hours 6 hours bedtime awakening 24 hours

time point

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 assignment (P 5 0.0298) and time point (P \0.0001).
efficiency included treatment, baseline chewing effi- Parameter estimates for this model are listed in Table I.
ciency, period, and prior treatment. For significant Contrasts were used to identify treatments that differed:
main effects, contrasts were used to identify the specific ibuprofen vs placebo (P 5 0.0034), and a borderline
groups that differred. For both outcomes, the impact of difference was seen between naproxen and the placebo
adding additional covariates (expected pain and sex) to (P 5 0.0563). Contrasts also indicated that all time pe-
the initial model was also examined. For all analyses, riods differed from each other (P \0.0001) except for
a P value less than 0.05 was considered statistically the T2 and T3 time points (P 5 0.41).
significant. SAS software (version 9.1, SAS Institute, The initial model for the VAS pain summary score was
Cary, NC) was used for the statistical analyses. evaluated to further identify treatment differences at
specific time points. Subjects who took ibuprofen re-
RESULTS ported significantly less pain than those who took the
The sample consisted of 11 women (46%) and 13 placebo at 2 and 6 hours after separator placement, as
men (54%); 75% were white, 13% Asian, 8% other, well as at bedtime and awakening. Acetaminophen
and 4% Hispanic. Their ages ranged from 19 to 30 years, and naproxen sodium did not show significant differ-
with a mean age of 26.4 years (SD, 2.5). Mean VAS pain ences compared with the placebo at any time point. By
summary scores by treatment groups and time points are 24 hours postplacement, which was 17 hours after the
displayed in the Figure. Our initial mixed model did not last medication dose, pain levels returned to those of
indicate significant effects due to period (P 5 0.85), the placebo for all subjects (P 5 0.27).
prior treatment (P 5 0.84), order (P 5 0.91), or time We next examined the impact of additional covariates:
point by treatment interaction (P 5 0.68). The reduced sex and expected pain. No significant effect in the VAS
model detected significant effects from treatment pain summary score due to sex was found (P 5 0.37).

American Journal of Orthodontics and Dentofacial Orthopedics January 2011  Vol 139  Issue 1
e56 Patel et al

Table I. Estimates of fixed effects from mixed model Table II. Estimates of the fixed effects from the mixed
analysis, with the dependent variable the VAS pain analysis for model including expected pain and
summary score expected pain by time interaction, with dependent
variable the VAS pain summary score
Parameter Estimate (SE) P value
Intercept 30.70 (2.70) \0.0001 Parameter Estimate (SE) P value
Treatment Intercept 21.45 (3.22) \0.0001
Ibuprofen 7.89 (2.59) 0.0035 Treatment
Naproxen sodium 5.04 (2.50) 0.0563 Ibuprofen 6.54 (2.46) 0.0103
Acetaminophen 3.67 (2.50) 0.1614 Naproxen sodium 3.45 (2.47) 0.1679
Placebo (reference) Acetaminophen 1.75 (2.49) 0.4853
Time point Placebo (reference)
2 hours 16,46 (1.42) \0.0001 Time point
6 hours 11.64 (1.32) \0.0001 2 hours 9.43 (2.27) \0.0001
Bedtime 10.90 (1.16) \0.0001 6 hours 5.92 (2.12) 0.0056
Awakening 5.74 (0.89) \0.0001 Bedtime 7.25 (1.88) 0.0001
24 hours (reference) Awakening 6.64 (1.45) \0.0001
24 hours (reference)
Expected pain 2.27 (0.48) \0.0001
Expected pain 3 time interaction
However, expected pain had a significant effect on the Expected pain 3 2 hours 1.99 (0.52) 0.0001
VAS pain summary score, and its impact varied over Expected pain 3 6 hours 1.62 (0.48) 0.0009
time. The coefficient estimates for this model are pre- Expected pain 3 bedtime 1.03 (0.43) 0.0157
sented in Table II. Considering both the impact of ex- Expected pain 3 awakening 0.26 (0.33) 0.4353
Expected pain 3 24 hours (reference)
pected 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 DISCUSSION
the subjects felt was consistent with their expectations. In this study, pain after separator placement was
For example, from the model, with all other factors equal, significantly related to the treatment drug and the
we could compare the predicted VAS pain summary score time after placement. Subjects who received ibuprofen
for a subject with an expected pain rating of 1.0 with that reported significantly less pain than those who received
of a subject with an expected pain rating of 7. The subject the placebo. These results are consistent with previous
with the higher expected pain rating (7) would have studies in support of ibuprofen before and after treat-
predicted VAS pain summary scores 1.7 points higher at ment.9,10,16,18 Bird et al,12 on the other hand, found
2 hours and 13.6 points higher at 24 hours, than the no significant differences in postseparator pain with
subject with the expected pain rating of 1. either acetaminophen or ibuprofen. In contrast to our
We analyzed the pain score further to examine indi- study, the drugs were administered only 1 hour before
vidual components (chewing, biting, fitting front teeth separator placement, with no follow-up doses. Polat
together, and fitting back teeth together). The results and Karaman11 studied several analgesics and recom-
were similar to the overall model for chewing, biting, mended acetaminophen over naproxen sodium or aspi-
and fitting back teeth together, with significant day rin. Although subjects who took naproxen sodium and
and treatment effects detected. However, significant aspirin felt almost no pain at 24 hours, the acetamino-
treatment effects were not seen for fitting the front teeth phen group showed similar pain scores, without the
together. side effects associated with NSAIDs.
For all treatment groups, chewing efficiency decreased Compared with the placebo, in this study, we found
markedly from T0 to T5. Considering chewing efficiency at significant differences only for ibuprofen, not naproxen
T5, the mixed model analysis indicated no significant sodium or acetaminophen. There were differences
differences from treatment assignment (P 5 0.36), prior between this study and that of Polat and Karaman11 in
medication (P 5 0.80), or period (P 5 0.88). However, regard to the drugs administered, dosing, and time;
the efficiency at T0 was a significant predictor of the the subjects’ ages; and the stimulus to induce pain.
performance at T5 (P 5 0.0131). Sex and expected pain Whereas 1100 mg of naproxen sodium was administered
rating did not affect chewing efficiency at T5. Mean chew- in the study of Polat and Karaman, only 750 mg were
ing efficiency at T0 was 46.6% (SD, 14.1%); this dropped used in our study. Our subjects were adults, and separa-
to 17.5% (SD, 14.6%) at T5. tors were used to induce pain. Subjects in the study

January 2011  Vol 139  Issue 1 American Journal of Orthodontics and Dentofacial Orthopedics
Patel et al e57

by Polat and Karaman were adolescents, and initial most pain medications do not reach high enough levels
archwires were placed to induce pain. in the blood to inhibit tooth movement. Several studies
The design of this study was well suited for studying have shown that the inhibition of prostaglandins by
pain relief. All previous studies on managing orthodontic NSAIDs does prevent or delay orthodontic tooth move-
pain with analgesics were parallel arm, in which each ment.24-27 It is important to consider the length of
subject received only 1 treatment. In our study, nonor- time these medications are taken and the amounts
thodontic subjects were selected, and, with the incom- administered. Short-term administration of NSAIDs
plete block crossover design, all subjects received 3 of will only temporarily affect prostaglandin levels; long-
the 4 possible treatments. Because of the subjective term use of these drugs should be avoided.5,26
nature of pain, within-subject assessment most likely Research showed that doses of 2400 to 3200 mg per
provided more power than parallel-arm studies. day of ibuprofen are required to achieve anti-
Pain scores at the different time points all signifi- inflammatory effects over analgesic effects.7 The doses
cantly differed from each other, with the exception of administered in this study did not reach anti-
T2 and T3. These results are comparable with those of inflammatory levels.
Steen Law et al9 and Bernhardt et al,16 who found no
differences in pain scores at 6 hours after treatment CONCLUSIONS
with ibuprofen. A recent study reported significantly Ibuprofen administered 1 hour before separator
less pain at 6 hours, bedtime, and awakening, with no placement, and 3 and 7 hours after placement, reduced
differences detected at 2 or 24 hours.10 Although in all postseparator placement pain compared with a placebo.
of these studies 400 mg of ibuprofen was administered Acetaminophen and naproxen sodium did not show
1 hour before separator placement, they varied on the significant differences compared with the placebo. The
postseparator placement doses. analgesic effects diminished by day 2, resulting in peak
For the T0 and T5 chewing efficiencies, no significant pain levels and decreased chewing efficiency at this
differences were seen among the treatment drugs. time. Additional drugs might be necessary to maintain
Significant differences are not expected, since the T0 pain relief. The expected pain also plays a role in experi-
chewing efficiency was before the administration of enced pain; subjects who expect more pain also report
drugs. By T5, the analgesic effects had dissipated with more pain.
the dosing regimen followed in the study.
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