|Year : 2014 | Volume
| Issue : 2 | Page : 44-49
Comparison of the analgesic effect of Ibuprofen and pulsed low-level laser in reducing pain after orthodontic separator placement and evaluation of the changes in the sulcular pain especially prostaglandin E2 level
Morteza Oshagh1, Hooman Zarif Najafi2, Fateme Bahramnia3, Behrouz Gharesi-Fard4
1 Orthodontist, Private Practice, Tehran, Iran
2 Department Orthodontic, Student Research Committee, Orthodontics Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
3 Orthodontist, Private Practice, Tehran; Department Orthodontic, Student Research Committee, Orthodontics Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
4 Department of Immunology, Infertility Research Center, Shiraz Proteomics laboratory, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
|Date of Web Publication||21-Nov-2014|
Department of Orthodontics, School of Dentistry, Orthodontics Research Center, Shiraz University of Medical Sciences, Shiraz
Source of Support: None, Conflict of Interest: None
Background : Non-steroidal anti-inflammatory drugs such as Ibuprofen have long been used as a relief to orthodontic pain, and low-level laser therapy (LLLT) has been recommended for the analgesic effects. Objective : The purpose of this study was to compare the analgesic effects of Ibuprofen and LLLT on orthodontic pain and prostaglandin E2 (PGE2) level assessment in gingival crevicular fluid (GCF). Subjects and Methods: A total of 28 volunteered dental students (14 male; 14 female) were randomly divided into LLLT group and Ibuprofen group. Maxillary first molars were randomly selected to place separators in mesial and distal contacts. One group received Ibuprofen administration and the other received pulsed low-level GaAlAs laser irradiation. GCF samples were collected before therapeutic interventions and 1 h and 24 h later. Pain intensity was analyzed before therapeutic intervention and 1 h and 24 h later using visual analogue scale (VAS). Statistical analyses were Mann-Whitney U-test, t-test, Friedman test, and repeated measures ANOVA test. Results: Based on VAS scores both groups experienced increasing pain within 24 h. A significant reduction was found in PGE2 levels after 1 h and an insignificant reduction after 24 h in Ibuprofen group, but in the laser group no significant change was observed in PGE2 levels (P < 0.05). Conclusions : The current study showed that pulsed low-level laser did not have any analgesic effect and Ibuprofen was most effective 1 h after administration. There was no difference in analgesic effects of laser and Ibuprofen, and no correlation was found between PGE2 levels of GCF and pain perception.
Keywords: Analgesic effect, gingival crevicular fluid, Ibuprofen, low-level laser, orthodontic pain, prostaglandin E2
|How to cite this article:|
Oshagh M, Najafi HZ, Bahramnia F, Gharesi-Fard B. Comparison of the analgesic effect of Ibuprofen and pulsed low-level laser in reducing pain after orthodontic separator placement and evaluation of the changes in the sulcular pain especially prostaglandin E2 level. J Dent Lasers 2014;8:44-9
|How to cite this URL:|
Oshagh M, Najafi HZ, Bahramnia F, Gharesi-Fard B. Comparison of the analgesic effect of Ibuprofen and pulsed low-level laser in reducing pain after orthodontic separator placement and evaluation of the changes in the sulcular pain especially prostaglandin E2 level. J Dent Lasers [serial online] 2014 [cited 2021 Oct 25];8:44-9. Available from: https://www.jdentlasers.org/text.asp?2014/8/2/44/145137
| Introduction|| |
According to orthodontic patients, pain is among the most common side effects of this treatment  and it is even comparable to the invasive dental procedures such as extractions.  Although the perception of pain differs from person to person, sometimes the severity urges the patients to cease treatment. 
Compression of periodontal ligament results in releasing of prostaglandins and cytokines which mediate pain. Based on this mechanism, anti-inflammatory medication such as Ibuprofen has been suggested as the gold standard to relief the orthodontic pain.  On the other hand, these drugs can adversely affect orthodontic tooth movement and also is contraindicated in patients with gastrointestinal and allergy problems. , In orthodontics, the analgesic effect of Ibuprofen has generally been used to reduce the post-adjustment pain and has been found effective on forced-induced pain relief. ,
The biostimulatory effects of low-level laser therapy (LLLT) have been studied since 1997,  and it has been shown that LLLT is an efficient technique in pain relief. , The pain inhibitory mechanism of LLLT is still under investigation, but there are evidence of nerve cell stimulation, stabilization of membrane potential, and the release of neurotransmitters in inflammatory tissues. ,, Of course, what should be taken in consideration is that LLLT when applied on both arches is a rather time-consuming procedure which can limit its clinical usage. 
One of the useful methods to assess the periodontal tissue response to orthodontic force is chemical analysis of gingival crevicular fluid (GCF).  Prostanoids are synthetized from arachidonic acid through cyclo-oxygenase pathway and are well-known mediators of inflammatory pain, especially prostaglandin E2 (PGE2). 
Since both drug therapy and laser therapy have their own advantages and disadvantages, performing a clinical comparison seems beneficial. Previous studies were only focused on studying the effect of LLLT on orthodontic induced pain , whereas this research compared and evaluated the effect of drug administration as well as LLLT. Furthermore, most studies have evaluated the effect of LLLT and Ibuprofen subjectively based on visual analogue scale (VAS), ,,, but this study additionally performed an immunological assessment of PGE2 in GCF, which seems to be more objective.
| Subjects and Methods|| |
The study consisted of 28 volunteer dental students of Shiraz Faculty of Dentistry (14 girls, 14 boys) with the age range of 18-28 years. The subjects were randomly divided into two equal groups: LLLT and Ibuprofen groups, using web site randomization program provided on www.randomizer.org. Each group consisted of 14 subjects (7 girls, 7 boys). Ethical approval for this study was obtained from an ethical committee of Shiraz University of Medical Science. The subjects were thoroughly informed, and consents were signed by them. The inclusion criteria of the study were as follow:
- Fully erupted second molars, presence of contact between all maxillary teeth and no history of extraction
- No caries or questionable dental treatments in the maxillary arch such as overhangs or suspicious endodontic treatments
- Healthy periodontal tissues (gingival index = 0 [Table 1], probing depth <3 mm, no periodontal attachment loss, and no evidence of periodontal bone loss in bitewing radiographs)
- No history of medical treatment that could affect the perception of pain
- No previous orthodontic treatment
- No history of contraindications or adverse reactions related to Ibuprofen in the medication group
- No use of antibiotics in Ibuprofen group
- Meeting a minimum weight requirement of 40 kg in Ibuprofen group.
Either right or left maxillary first molar was randomly selected, and orthodontic separators (Dentaurum, Germany) were placed by a post graduate student of orthodontics at mesial and distal contact of the tooth.
Gingival cervical fluid sampling
Gingival hygiene was evaluated with Lφe gingival index [Table 1].  The measured indexes were registered in patient's records. For the evaluation of quantities of the signified cytokine, GCF was collected from the mesiobuccal, mesiopalatal, distobuccal, and distopalatal gingival crevice of each subject.
The subjects brushed their teeth before sampling. The tooth was washed, isolated, and gently dried. Paper strips (Periopaper; ProFlowInc, Amityville. NY) were inserted 1 mm into the gingival crevice for 30 s and then removed.
To increase the amount of GCF, a second strip was inserted, in the same way, after 1 min. The eight paper strips were sealed in a 2 ml microtube (Watson, Japan) and immediately frozen at −80°C until the day of analysis. In instances of visible contamination with blood, the strips were discarded. The lab technician was not recognized whether they are LLLT or Ibuprofen group.
Low level laser therapy group
A GCF sample was collected before separator placement (PT1), and then separators were placed on randomly selected maxillary molars. The teeth were irradiated using an 820 nm GaAlAs diode laser (THOR, DD2_England) with an output power of 50 mW in orthodontic department of Shiraz dental school. The irradiation was performed for 5 s with pulsing waves by a fiber applicator (2 mm in diameter) on four points (mesiobuccal, mesiopalatal, distobuccal, and distopalatal) around the tooth [Table 2]. After that, the second sample was collected 1 h after separator placement (PT2). 24 h later, GCF collection was repeated (PT3).
A GCF sample was collected before separator placement (PT1) and Ibuprofen administration. The subjects were administered only one tablet of ibuprofen, 400 mg 1 h prior to separator placement. The second sample was collected 1 h after separator placement (PT2). 24 h later, GCF collection was repeated (PT3).
Visual analogue scale scoring
All subjects were asked to record their pain level (by marking a point) on a 100 mm VAS sheet before separator placement (VT1), 1 h (VT2) and 24 h (VT3) after separator placement. The marked point was measured with a 10 cm ruler in millimeters. Each millimeter was given a VAS score of 1, so that the score of 0 at the left end of the scale indicated no pain, the score of 100 at the right end of the scale was regarded as maximum pain, and the score of 50 in the center indicated moderate pain.
Determination of prostaglandin E2 levels by enzyme-linked immunosorbent assay kits
On the day of analysis, 200 μL of Hank's buffered salt solution containing 1% bovine serum albumin (Sigma, St. Louis, MO) was added to the tubes containing the sample strips. The tubes were gently shaken for 1 min and then centrifuged at 2000 rpm for 5 min.
Then the strips were removed. The amount of PGE 2 was determined using enzyme-linked immunosorbent assay (ELISA) assay (Shanghai Crystal Day, China) in accordance with the manufacturer's instructions. After performing the ELISA test, the optical density was measured using an ELISA reader (Anthos 202 Micro Plate reader, Austria) set to a wave-length of 450 nm. The PGE 2 levels in GCF were calculated from the standard curves and defined as picograms/site for total cytokine levels. Sites with cytokine levels below the limits of the kit's detectability were scored as 0.
Data analysis was performed by SPSS for Windows, version 18 (Hong Kong, Westlands Centre). Means and standard deviations at each time interval were calculated as the descriptive statistics for VAS scores and PGE 2 levels. Mann-Whitney U-test and t-test were used to compare differences in mean pain scores and PGE 2 levels between the groups. The intra-group comparisons of VAS for different time intervals were analyzed by using the Friedman test and repeated measures ANOVA test for PGE2. The level of significance was set at P < 0.05.
| Results|| |
Statistical analyses revealed that PGE2 levels at PT1, PT2 and PT3 were found as 276.18, 241.90 and 269.77 pg/site for Ibuprofen group and 249.48, 246.15 and 261.96 pg/site for the laser group, respectively. The difference among measurements between PT1 and PT2 in Ibuprofen group was statistically significant (P = 0.014), whereas there were no differences between PT2 and PT3, PT1 and PT3 (P > 0.05). In laser group the difference among measurement was not significant (P > 0.05) [Table 3].
The results showed that mean VAS scores at VT1, VT2, VT3 were as 0 ± 0, 2.1 ± 5.7, and 17.8 ± 27.7 for Ibuprofen group and 0 ± 0, 1.4 ± 5.3, and 12.1 ± 25.1 for the laser group, respectively. The difference between measurements was found to be statistically significant in each group (P < 0.05) [Table 4].
|Table 4: Intra-group comparisons of VAS scores at different time intervals |
Click here to view
Comparison of PGE2 levels between two groups at three different time revealed that there was no significant difference (P < 0.05) [Figure 1]. Intergroup analyses of VAS showed that there was no difference between two groups (P < 0.05) [Figure 2].
| Discussion|| |
Many researchers have studied analgesic effects of Ibuprofen and LLLT. ,,, There are also various means of measurement that can be either subjective or objective. VAS is a subjective parameter that was used in many studies, ,, nevertheless some bias is inevitable due to its subjective nature. The basic mechanism of orthodontic pain is acute inflammatory responses in the periodontal ligament.  To mimic this mechanism we placed separators between dental contacts. According to Kess et al. Prostaglandins level increase and reach a peak 24 h after force application.  It seems that prostaglandins cause some sort of hyperalgesia. Another suggested mediator is substance P that likely peaks 36 h after separator placement.  Therefore in this study, an immunological assessment of PGE2 in GCF was also accomplished, which is more objective along with a VAS form to take subjects' opinion into consideration.
The subjects of this study were volunteered dental students. On one hand the subjects were not selected randomly, but, on the other hand, being dental students has a great impact on their attitude and pain perception. This might be beneficial to this research since being volunteers excludes individuals with lower pain threshold and dental fears.
Although the measurement intervals and the peak periods are different, according to some studies orthodontic pain resulting from heavy forces such as separator placement commences 2 h after application and reaches a peak level after 18-24 h. ,, In our study, the VAS scores and PGE2 levels were evaluated once before any intervention and 1 h then 24 h after separator placement.
The basic design of this study is somehow different. The previous studies used a split-mouth technique to eliminate the effect of the inter-person variability of pain perception.  What should be taken into consideration is that orthodontic pain has a generalized nature, and this may cause bias in the results.  On the other hand, split-mouth technique can only be used for local treatment notions such as laser irradiation whereas Ibuprofen has a systemic effect which makes split-mouth technique impossible.
In orthodontics, the analgesic effect of LLLT has been used to reduce post-adjustment pain and has been found effective. , Another study suggested that LLLT has no effect on pain intensity and prevalence and the observed reduction in pain levels may be a true placebo effect (howthorne effect).  Based on the previous study we used GaAlAs low-level laser and applied it on four points of the teeth, each point was irradiated for 5 s.  The only difference of this study was that the beam was functioning in a pulse mode. Pulse mode has some benefits over continuous mode. It has been proven that when irradiating deep parts of the tissue higher energy is delivered by the device that may increase tissue temperature and cause thermal damage. Such irritations are much less when the laser beam is functioning in pulse mode.  Therefore, any comparison between this study and previous ones should be performed cautiously due to the difference in design. There is little evidence about the effect of different types of the laser beam on pain relief. However, there are studies that compare the effects of continuous waves and pulsed waves on orthodontic tooth movement. Some showed that there was no difference in tooth movement,  and others claimed that pulse mode would accelerate tooth movement.  Unlike previous studies, this study used a pulse mode GaAlAs and PGE2 analysis showed an insignificant decrease in PGE2 levels after 1 h and an insignificant increase after 24 h.
Overall, we can conclude that pulse mode LLLT doesn't have a significant anti-inflammatory effect on periodontal tissue. These findings also correlate with the patients' VAS forms in which they claimed to develop higher degrees of pain 1 and 24 h after separator placement. There are studies that have assessed the effect of low-level laser on pain inhibition not otherwise focusing on dental pain. One of them reported that low-level pulsed laser doesn't seem to have inhibitory effects on ischemic pains  that are also a possible mechanism in periodontal pain. Craig et al. proved that LLLT has no analgesic effects on muscular pain. 
The anti-inflammatory effect of Ibuprofen is well proven, and it has been used to relief orthodontic pain.  According to our results administration of Ibuprofen causes a significant decline in PGE2 levels after 1 h and an insignificant decrease after 24 h, but subjects reported increased pain after 1 and 24 h. In accordance with our results, Tunηer suggested that there may be no relation between PGE2 levels and perception of pain.  This also may indicate that a single dose of Ibuprofen is not simply enough to relief the pain that is in agreement with Bird et al. 
According to our results, there was no significant difference between laser application and Ibuprofen administration neither in subjective nor in objective results. No previous study has compared analgesic effects of Ibuprofen and LLLT, therefore, further investigation is required. Regarding the fact that laser therapy is a rather expensive treatment modality and is harder to obtain and also to consider the better results by Ibuprofen administration, Ibuprofen seems to be a cheaper, simpler and rather cost-effective treatment option in patients who can tolerate it. According to the text books, infrequent use of lower doses of Ibuprofen doesn't have any adverse effect on tooth movement.  On the other hand, many studies have revealed that applying LLLT reduces the pain , but, none of them has compared the effects of laser beam types, which may affect the results and merit more research.
| Conclusions|| |
Pulsed low-level laser did not have any analgesic effect. Ibuprofen was most effective 1 h after administration. There was no significant difference between ibuprofen and LLLT analgesic effect. There was no relationship between PGE2 levels and pain perception.
| References|| |
Oliver RG, Knapman YM. Attitudes to orthodontic treatment. Br J Orthod 1985;12:179-88.
Jones M, Chan C. The pain and discomfort experienced during orthodontic treatment: A randomized controlled clinical trial of two initial aligning arch wires. Am J Orthod Dentofacial Orthop 1992;102:373-81.
Glick J, Irondi K, Kamji Z, Kim P, McAllister J, Nguyen H. Orthodontic Pain Management. University of Toronto: Faculty of Dentistry; 2009.
Xiaoting L, Yin T, Yangxi C. Interventions for pain during fixed orthodontic appliance therapy. A systematic review. Angle Orthod 2010;80:925-32.
Chumbley AB, Tuncay OC. The effect of indomethacin (an aspirin-like drug) on the rate of orthodontic tooth movement. Am J Orthod 1986;89:312-4.
Tunçer Z, Polat-Ozsoy O, Demirbilek M, Bostanoglu E. Effects of various analgesics on the level of prostaglandin E2 during orthodontic tooth movement. Eur J Orthod 2014;36:268-74.
Bird SE, Williams K, Kula K. Preoperative acetaminophen vs ibuprofen for control of pain after orthodontic separator placement. Am J Orthod Dentofacial Orthop 2007;132:504-10.
Mester E, Spiry T, Szende B, Tota JG. Effect of laser rays on wound healing. Am J Surg 1971;122:532-5.
Moore CK, Hira N, Broome IJ, Cruikshank JA. The effect of infra-red diode laser irradiation on the duration and severity of post-operative pain: A double blind trial. Laser Ther 1992;4:145-8.
Soriano F, Rios R. Gallium arsenide laser treatment of chronic low back pain: A prospective, randomized and double-blind study. Laser Ther 1998;10:175-80.
Turhani D, Scheriau M, Kapral D, Benesch T, Jonke E, Bantleon HP. Pain relief by single low-level laser irradiation in orthodontic patients undergoing fixed appliance therapy. Am J Orthod Dentofacial Orthop 2006;130:371-7.
Fork RL. Laser stimulation of nerve cells in Aplysia. Science 1971;171:907-8.
Ponnudurai RN, Zbuzek VK, Wu WH. Hypoalgesic effect of laser photobiostimulation shown by rat tail flick test. Acupunct Electrother Res 1987;12:93-100.
Tortamano A, Lenzi DC, Haddad AC, Bottino MC, Dominguez GC, Vigorito JW. Low-level laser therapy for pain caused by placement of the first orthodontic archwire: A randomized clinical trial. Am J Orthod Dentofacial Orthop 2009;136:662-7.
Offenbacher S, Farr DH, Goodson JM. Measurement of prostaglandin E in crevicular fluid. J Clin Periodontol 1981;8:359-67.
Kawabata A. Prostaglandin E2 and pain - an update. Biol Pharm Bull 2011;34:1170-3.
Carranza FA, Newman MG, Takei H. Carranza's Clinical Periodontology. 10 th
ed. Canada: WB Saunders; 2006. p. 115.
Artés-Ribas M, Arnabat-Dominguez J, Puigdollers A. Analgesic effect of a low-level laser therapy (830 nm) in early orthodontic treatment. Lasers Med Sci 2013;28:335-41.
Yamasaki K, shibata Y, Fukuhara T. The nature of pain reaction associated with orthodontic tooth movement. J Jpn Orthod Soc 1985;44:332-8.
Kess B, Zwilling B, Lanese R, Shanfeld J, Davidovitch Z. The effect of indomethacin on periodontal PGE content during orthodontic treatment. J Dent Res 1987;66:332.
Lim HM, Lew KK, Tay DK. A clinical investigation of the efficacy of low level laser therapy in reducing orthodontic postadjustment pain. Am J Orthod Dentofacial Orthop 1995;108:614-22.
Bicakci AA, Kocoglu-Altan B, Toker H, Mutaf I, Sumer Z. Efficiency of low-level laser therapy in reducing pain induced by orthodontic forces. Photomed Laser Surg 2012;30:460-5.
Hashmi JT, Huang YY, Sharma SK, Kurup DB, De Taboada L, Carroll JD, et al. Effect of pulsing in low-level light therapy. Lasers Surg Med 2010;42:450-66.
Duan J, Na Y, Liu Y, Zhang Y. Effects of the pulse frequency of low-level laser therapy on the tooth movement speed of rat molars. Photomed Laser Surg 2012;30:663-7.
Kim SJ, Moon SU, Kang SG, Park YG. Effects of low-level laser therapy after Corticision on tooth movement and paradental remodeling. Lasers Surg Med 2009;41:524-33.
Mokhtar B, Baxter GD, Walsh DM, Bell AJ, Allen JM. Double-blind, placebo-controlled investigation of the effect of combined phototherapy/low intensity laser therapy upon experimental ischaemic pain in humans. Lasers Surg Med 1995;17:74-81.
Craig JA, Barlas P, Baxter GD, Walsh DM, Allen JM. Delayed-onset muscle soreness: Lack of effect of combined phototherapy/low-intensity laser therapy at low pulse repetition rates. J Clin Laser Med Surg 1996;14:375-80.
Proffit WR, Field HW, Sarver DM. Cotemporary Orthodontics. 5 th
ed. Canada: Elsevier; 2013. p. 289.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]