International Journal of Oral & Maxillofacial Surgery
Volume 39, Issue 6 , Pages 580-584, June 2010

Efficacy of nimesulide versus meloxicam in the control of pain, swelling and trismus following extraction of impacted lower third molar

  • S.A.F. De Menezes

      Affiliations

    • Department of Periodontics, University Center of Pará, Avenida Nazaré 630, CEP: 66035170 (Nazaré), Belém, Pará, Brazil
    • ,
  • P.R. Cury

      Affiliations

    • Department of Periodontics, School of Dentistry, Federal University of Bahia, Av. Araújo Pinho, 62. Canela, CEP 40110-150, Salvador, Bahia, Brazil
    • Corresponding Author InformationAddress: Patricia Ramos Cury, Av. Araújo Pinho, 62, Canela CEP: 40110-150, Salvador/Bahia. Tel.: +55 71 3336 8993; fax: +55 71 3336 5776.

Accepted 16 March 2010. published online 22 April 2010.

Article Outline

Abstract 

This study compared the efficacy of nimesulide and meloxicam in the control of pain, swelling and trismus, following the extraction of impacted inferior third molars. Twenty patients with two impacted inferior third molars, in similar positions, were selected. The patients were designated randomly to the meloxicam group (MEL: 7.5mg twice a day for 5 days) or the nimesulide group (NIM: 100mg for 5 days). Following the extractions, swelling was more pronounced in the MEL group than in the NIM group (P≤0.001). There were no significant differences in pain intensity between the treatment groups (P>0.05). At the 72-h evaluation, reduction was significantly larger in mouth opening in the MEL group compared with the NIM group (P<0.05). In conclusion, pain control was similar in both treatment groups. NIM was more effective than MEL in the control of swelling and trismus following the extraction of impacted lower third molars.

Keywords: pain, trismus, edema, non-steroidal anti-inflammatory drugs

 

Inflammatory response is mediated by prostaglandins, the synthesis of which is initiated by the release of arachidonic acid from membrane phospholipids. The subsequent conversion of arachidonic acid to prostaglandin is catalyzed by cyclooxygenases (COX). There are two known isoforms of this enzyme, COX-1 and COX-2. Whilst COX-1 is expressed constitutively in most tissues for homeostatic functions, an array of stimuli, including inflammation, injury and mechanical stress, trigger the synthesis of COX-2, which, in consequence, induces the production of pro-inflammatory prostaglandins9. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, and are prescribed for pain relief and edema control following most oral surgery.

NSAIDs are categorized into four groups according to their efficacy as inhibitors of COX-1 and/or COX-2: selective COX-2 inhibitors (e.g. rofecoxib, NS-389); preferential COX-2 inhibitors (e.g. etodolac, meloxicam, nimesulide, celexoxib); NSAIDs with relatively poor selectivity (e.g. diclofenac, piroxicam); NSAIDs with weak inhibition of both COX-1 and COX-2 (e.g. many of the salicylates)8.

It has been claimed that meloxican (MEL) and nimesulide (NIM) are preferential inhibitors of 3- to 12-fold selectivity for COX-2 over COX-1 in vitro6, 13. Recent studies have demonstrated the efficacy of MEL in controlling postoperative pain, swelling and trismus after the removal of impacted third molars1, 3. NIM has also been found to alleviate postoperative pain and swelling after maxillofacial surgery, such as that for the removal of third molars7, 18. In contrast to MEL, the effect of NIM on trismus control has not been evaluated.

The aim of the present study was to compare the efficacy of two NSAIDs, NIM and MEL, in controlling postoperative pain, swelling and trismus following the extraction of impacted lower third molars.

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Methods 

The protocol of the present study was approved by the Institutional Ethics Committee. The subjects were selected from a pool of patients admitted for regular dental treatment between January and September 2005. All participants, or their legal guardians, signed an informed consent form.

The study protocol involved a screening consultation followed by initial therapy to ensure gingival health and to establish the optimal biofilm control, surgical therapy and post-surgical examinations.

Twenty healthy, non-smoking patients (11 males and 9 females; mean age±standard deviation: 20.3±2.66 years) without contraindications to oral surgery and not taking any medication, who were to undergo surgical removal of bilateral and symmetrically placed impacted lower third molars were enrolled in the study. Orthopantomographic radiograms were taken to ensure the similarity of the tooth inclinations according to Winter's classification (vertical, mesioangular and distoangular positions)23. The impaction of the teeth was categorized as fully or partially bone-impacted.

A single examiner performed all clinical measurements prior to surgery (baseline) and 24, 48 and 72h postoperatively (Fig. 1). Swelling measurements were taken using a 2-0 nylon thread (Ethicon, Johnson & Johnson, São Paulo, SP, Brazil) and a millimeter ruler, and trismus measurements were made using a Willis caliper. To evaluate the swelling, markings with permanent marker were made prior to the surgery on the following facial regions: the angle of the mandible, the tragus, the labial commissure, the nasal border, laterally to the external corner of the eye, and on the soft pogonion. The following measurements were taken: Distance I; Distance II; Distance III; Distance IV; Distance V (Fig. 1)12. Trismus was evaluated by measuring the distance between the incisal edges of the upper and lower central incisors (Distance VI)11. The sensation of pain was evaluated in the periods 8–12h, 12–24h and after 24h postoperatively using a verbal rating scale16, in which the patients indicated the intensity of pain according to six descriptive scores (1: no pain, 2: mild pain, 3: moderate pain, 4: severe pain, 5: very severe pain, 6: extreme pain). The amount of the analgesic, acetaminophen 750mg (Tylenol®, Cilag Farmacêutica Ltda, São Paulo, SP, Brazil) taken in the periods 8–12h, 12–24h and after 24h postoperatively was also recorded. Gastrointestinal adverse events were registered on the patients’ charts.

  • View full-size image.
  • Fig. 1. 

    Distances used for the evaluation of postoperative swelling: from the angle of the mandible to tragus (Distance I); from the angle of the mandible to the external corner of the eye (Distance II); from the angle of the mandible to the nasal border (Distance III); from the angle of the mandible to the labial commissure (Distance IV); and from the angle of the mandible to the soft pogonion (Distance V).

According to the randomized, double-blind and crossed design of the study, bilateral molars were assigned randomly by the toss of a coin to either the MEL group (7.5mg) or the NIM group (100mg). Both drugs, kept in appropriate receptacles with a green or red label, were administered orally 1 hour before surgery, 12h after the first dose, and thereafter once a day for 5 consecutive days.

Extra-oral antisepsis was performed with 2.0% chlorhexidine solution, and intraoral antisepsis with a 0.12% chlorhexidine rinse (Proderma Farmácia de Manipulação Ltda, Piracicaba, SP, Brazil). The nerve block of the inferior alveolar, lingual and buccal nerves was carried out using 2.0% lidocaine with 1:100,000 epinephrine (Lidocaína-Alphacaina, Adrenalina 1:100,000, DFL Ind. E Com. Ltda, Rio de Janeiro, RJ, Brazil). The surgery to remove the lower third molar followed the standardized technique. Briefly, an ‘L’ shaped incision was made, and a mucoperiosteal flap was elevated. When osteotomy and tooth section were performed on one side, the other side received the same treatment in order to standardize the surgical trauma. All procedures were performed under abundant irrigation with a sterilized 0.9% physiological solution.

During the first days after the surgery, the patients were authorized to take analgesics (acetaminophen 750mg four times daily) (Tylenol®, Cilag Farmacêutica Ltda, São Paulo, SP, Brazil) only in case of pain. They were instructed to eat only soft food, and to abstain from mouth washing during the first 24h and from brushing and flossing around the surgical area until suture removal (14 days post-surgery). For plaque control, patients used a 0.12% chlorhexidine mouth rinse for 1min twice a day for 2 weeks postoperatively.

The minimum interval between the removal of the first and the second impacted lower third molar was 15 days.

The Student–Newman–Keuls test or the Wilcoxon test was used to investigate potential differences within each treatment group and between the two groups. The χ2-test was used to assess the relationship between pain score and tooth impaction, and between pain score and tooth position. A one-way ANOVA, followed by a post hoc T-test or a Tukey-test, was used to compare the amount of analgesic used by the patients in relation to teeth impaction and the position, respectively.

The level for a significant difference was set at P≤0.05. Calculations were performed using the SPSS statistical software package (SPSS Inc., Chicago, IL, USA).

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Results 

All patients complied with the study protocol, tolerated the surgical procedures well, and completed the follow-up period. Neither gastrointestinal adverse events nor postoperative complications occurred during the study.

In both treatment groups, a significant increase in swelling was observed after surgery for all measurements taken (P≤0.001) (Table 1). In general, the MEL group presented more pronounced swelling than the NIM group. The differences between both drugs were statistically significant after 24h for Distance II, after 48h for Distances II and V, and after 72h for all distances measured (P≤0.03) (Table 1).

Table 1. Differences between the measurements prior to surgery and those made 24, 48 and 72h postoperatively at distances: I (from angle of the mandible to tragus), II (from angle of the mandible to external corner of the eye), III (from angle of the mandible to nasal border), IV (from angle of the mandible to labial commissure) and V (from angle of the mandible to soft pogonion) in the meloxicam (MEL) and nimesulide (NIM) groups. Values are mean±SD in mm.
DistanceIIIIIIIVV
MELNIMMELNIMMELNIMMELNIMMELNIM
24h1.7±1.3a,b1.8±1.7a,b3.9±2.0a,b3.1±1.6a,b,*5.3±4.1a,b3.9±2.2a,b5.2±4.14.9±3.2a4.2±3.4a,b3.1±2.2a,b
48h3.3±2.2c2.6±2.0c6.2±2.3c4.5±2.5c,*7.3±3.5c6.1±2.2c9.0±5.2c7.4±3.6c6.5±3.4c4.9±2.2*
72h5.5±3.93.3±2.4*8.4±3.25.7±3.1*10.5±3.57.3±2.5*12.4±5.59.4±3.3*9.4±4.06.5±2.7*

aDifference between 24 and 48h values statistically significant (P≤0.001).

bDifference between 24 and 72h values statistically significant (P≤0.001).

cDifference between 48 and 72h values statistically significant (P≤0.001).

*Statistically significant difference between the drugs (P≤0.03).

In both groups, the pain intensity was significantly higher 8–12h post-surgery than in the interval 12–24h and after 24h (P≤0.003) (Fig. 2). No patients had pain or used analgesics after 24h . The tendency for analgesic intake was higher in the first observation period than in the second (P=0.08). There was no significant difference in pain intensity between the MEL and NIM groups (P>0.05) and patients in both groups used a similar average amount of analgesics (8–12h, MEL 2.55±1.09 capsules, NIM 2.2±0.83 capsules, P=0.23; 12–24h, MEL 1.70±1.12 capsules, NIM 1.35±0.49 capsules, P=0.86) (Table 2). Postoperative pain and analgesic intake did not differ between patients with partially or fully bone-impacted teeth, and were independent of the inclination of the third molars (P>0.05).

Table 2. Analgesic intake in the meloxicam (MEL) and nimesulide (NIM) groups. Values are mean±SD in mg taken by the patients.
GroupNAnalgesic intake
8–12h12–24hAfter 24h
NIM201650±622.5*1012.5±300*0
MEL201912.5±750*1275±840*0

*P≤0.05: 8–12h versus after 24h; 12–24h versus after 24h.

After removal of the third molars, a significant decrease in mouth opening was observed in patients from both treatment groups (P≤0.01) (Fig. 3). This reduction in mouth opening was significantly larger in the MEL group than in the NIM group 72h after surgery (P=0.03). At the other evaluation points, 24 and 48h postoperatively, the difference between the treatment groups was not significant (P>0.05) (Table 3).

Table 3. Reduction in mouth opening (trismus) (mean±SD, in cm) between the baseline (measurements prior to the surgery) and 24, 48 and 72h postoperatively, in the meloxicam (MEL) and nimesulide (NIM) groups.
GroupNBaselineMaximal mouth openingReduction of mouth opening
24h48h72h24h48h72h
NIM204.04±0.652.76±0.822.61±0.662.64±0.62*1.27±0.751.43±0.771.39±0.72*
MEL204.04±0.652.57±0.692.44±0.642.33±0.611.47±0.531.59±0.511.70±0.52

*Statistically significant difference between the two groups (P=0.03).

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Discussion 

The aim of the present study was to compare the analgesic and anti-inflammatory efficacy of 7.5mg MEL with that of 100mg NIM in patients undergoing surgical extraction of both third molars. To the authors’ knowledge, this is the first study focusing on the analgesic and anti-inflammatory efficacy of pre- and postoperatively administered MEL and NIM, and the first report on the effect of NIM on trismus.

In the present study, a significant increase in swelling was observed until 72h after the removal of the third molars. These results differ from the data reported by Troullos et al.22 who observed maximum facial swelling 48h after the surgical procedure. The distance between the angle of the mandible and the labial commissure (Distance IV) was most affected by the swelling, which is in agreement with a previous study by Bastos et al.2.

Postoperative swelling was more pronounced in the MEL group than in the NIM group. NIM has been shown to be superior to other NSAIDs for the control of postoperative swelling. A double-blind comparison of NIM and ketoprofen demonstrated that NIM (200mg, administered rectally twice a day) was more effective and more rapid than ketoprofen (100mg, rectally twice a day) in reducing swelling and hyperaemia associated with the surgical removal of impacted third molars.7 NIM (100mg, orally twice a day) was considered more efficient than naproxen (250mg, orally twice a day) for the reduction or prevention of swelling and hyperaemia in the postoperative treatment of inflammatory complications due to maxillofacial surgery7. An important advantage of MEL is that it does not delay bone healing15. It is not known whether NIM delays bone healing.

Various methods have been used to measure facial swelling. The method employed in this study is not as accurate as computed tomography scans or magnetic resonance imaging, but it is a non-invasive, simple, cost-effective and timesaving method of obtaining numeric values for the determination of soft tissue contour changes3.

Postoperative pain was evaluated using a verbal rating scale and determining the amount of analgesic used by the patients in the first 24h postoperatively. Postoperative pain was of short duration and reached its maximum intensity in the early postoperative period (8–12h), which is in agreement with Seymour et al.21. Concerning the analgesic efficacy of MEL and NIM, there was no significant difference between the pain scores obtained in both treatment groups. Different studies have compared the analgesic efficacy of MEL and NIM to that of other anti-inflammatory drugs. Pre-emptive 10mg MEL, for instance, was more effective than 27mg ampiroxicam1. NIM (200mg) was more effective than ketoprofen (100mg) administered postoperatively twice a day for 5 days18. There was no difference in analgesic efficacy between single doses of either 100mg NIM, 200mg NIM, or 250mg nuflemic acid, administered orally after surgery19. Rofecoxib 50mg/day for 6 days resulted in significantly better analgesia than NIM 200mg/day following dental surgery. In that study, none of the patients used additional analgesics, which indicates that both NIM and rofecoxib were effective analgesically.

In the present study, the amount of analgesic used by the patients and postoperative pain did not differ between cases of full or partial bone impaction, or between different inclinations of the third molar. In contrast, Calvo et al.3 observed an elevated analgesic intake in patients who underwent third molar surgery with osteotomy compared with those who did not require osteotomy; all of them received 7.5mg MEL. In that study, the patients only received MEL postoperatively, whereas in the present study, MEL and NIM were administered both pre- and postoperatively. It has been demonstrated that the preoperative administration of NSAIDs is more effective in pain control than their postoperative administration5, 14. When administered preoperatively, NSAIDs prevent peripheral sensitization, which is an increase in the sensitivity of peripheral nociceptors induced by inflammatory mediators, such as prostaglandins, which are released locally at the site of injury. As a consequence of reducing the synthesis of prostaglandins, COX inhibitors prevent the nociceptors becoming sensitized to chemical and mechanical stimuli4.

It has been suggested that trismus is the result of a protective reflex against inflammatory states of orofacial tissues24 and avoids maximum mouth opening by the patient due to postoperative pain17. In the present study, trismus control was superior in the NIM group compared with the MEL group. The lower use of analgesics in the NIM group (although not statistically significant) suggests that the patients in this group suffered less from pain than the MEL treated patients. This may explain the wider mouth opening in the NIM group.

Considering that NIM was more effective than MEL in the control of swelling and trismus following the removal of impacted lower third molars, the results suggest that the anti-inflammatory effect of NIM is superior to that of MEL. In addition to preferentially inhibiting the production of prostaglandins (especially PGE2) by cyclooxygenase-2 (COX-2), there is evidence that NIM has additional features important for suppressing inflammatory processes. It has been demonstrated that NIM inhibits the release of histamine from mast cells and basophils, as well as the release of hydroxyl radicals, superoxide radicals and the production of hypochlorous acid by activated polymorphonuclear neutrophil leucocytes. It has been suggested that NIM suppresses the release or production of histamine, leukotrienes, pro-inflammatory cytokines and the release of enzymes by leucocytes. It may prevent the synthesis of platelet-activating factors from activated platelets and other cells, and the production of metalloproteinases. NIM activates glucocorticoid receptors, leading to elevated cellular activity of endogenous glucocorticoids, which seems to be a unique effect of this NSAID20.

The authors did not formally evaluate the safety and tolerability of the drugs investigated, but the patients did not report any adverse events. A review of hepatic adverse events demonstrated that the number and severity of hepatotoxic events were substantially higher for NIM than for other NSAIDs10. In that study, the patients who showed an elevated risk for NIM-related hepatotoxicity were older, of female gender, and the average treatment time had been 62 days. In the present study, by contrast, the participants were young (about 20 years old) and used NIM only for a short period of time, which may explain the observed tolerability.

In conclusion, NIM was more effective than MEL in the control of swelling and trismus following the removal of impacted lower third molars. Pain control did not differ between the drugs. More studies with larger groups are required to clarify this study.

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Competing interests 

None declared.

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Funding 

Dr. Cury is supported by The National Council for Scientific and Technological Development-CNPQ (304733/2006-7).

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Ethical approval 

The study protocol was approved by the Institutional Ethics Committee.

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Acknowledgement 

The authors acknowledge Dr Franco Arsati for writing assistance.

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References 

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PII: S0901-5027(10)00106-2

doi:10.1016/j.ijom.2010.03.012

International Journal of Oral & Maxillofacial Surgery
Volume 39, Issue 6 , Pages 580-584, June 2010

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