The effects of ibuprofen and acetaminophen on orthodontic pain control and interleukin-1β levels in gingival crevicular fluid

 

 

Abstract              Background: Pain is one of the unpleasant experiences occurring during orthodontic treatment. Non Steroidal Anti Inflammatory Drug (NSAIDs) having analgesic properties minimizes discomfort caused by appliance activation. Acetaminophen with weak anti-inflammatory action, is effective in relieving discomfort without hampering Orthodontic tooth movement (OTM). Interleukin -1 β (IL-1β) a potent pro-inflammatory cytokine is reflected in Gingival Crevicular Fluid (GCF) during OTM. The study objective is to determine and evaluate effects of Ibuprofen and Acetaminophen on orthodontic pain control and IL-1β levels in GCF during initial stages of OTM. Methodology: A total of 30 subjects were divided into three equal groups. Initial levelling and aligning stage were carried out using 0.014’’ NiTi. First and second group were prescribed with Ibuprofen and Acetaminophen respectively. Third group was control. Subjects were advised to rate average daily pain quality at (P₁)24 hours, (P₂) 48hours, (P₃)72 hours and (P₇)168 hours in all the groups. GCF samples were obtained at four time points and IL-1β levels were evaluated and correlated with pain scores. GCF samples were assayed with commercially available human IL-1β Enzyme-Linked Immunosorbent Assay (ELISA) kit. Results: IL-1β levels in all the groups increased significantly by 24 hours(T₁) from their respective baseline levels, decreased by (T₂)48 hours and eventually reached close to baseline levels by 168 hours(T₃). No Statistically significant correlation was found between drug groups at 48 hours(T₂). There was statistically significant correlation in all the groups at 24 hours, 168 hours. Negative correlation was found between IL-1β levels and pain scoring in drug groups indicating that IL-1β levels increased as OTM progressed, but pain decreased. Positive correlation was found between the two in control group. Conclusions: Ibuprofen and Acetaminophen have an inhibitory effect on the IL-1β levels and thereby cause impediment to rate of tooth movement. However, they decrease orthodontic pain during initial stages of treatment.

               Keywords: Pain, Ibuprofen, Acetaminophen, IL, GCF, ELISA

 

INTRODUCTION

Orthodontics being a fast-growing speciality is aimed at achieving good functional occlusion and a perfect smile. During treatment, pain has been rated as the greatest dislike and fears and apprehensions prior to orthodontic treatment.¹ Orthodontic pain is the discouraging aspect of the treatment, is one of the primary reasons to discontinue the treatment. During treatment, patients often describe the discomfort as tension, ache, pressure or soreness of the teeth. About 90-95% of the patients undergoing orthodontic treatment report pain with appliances.³ Pain perception is part of an inflammatory reaction causing alterations in blood flow following orthodontic force application.⁴ Pain scale is a tool that is used to help assess a person’s pain. In response to external stimuli, cytokines are actively secreted by diverse cell types and are diminutive protein molecules that regulate cell communication and function by inducing cellular proliferation and differentiation.^5,6  Interleukin (IL)-1, is a cytokine which exists in two forms alpha and beta of which in bone metabolism interleukin-1β is form pertinent.⁷  In gingival crevicular fluid (GCF), inflammatory phenomena during tooth movement could be found where significant elevations in the concentrations of inflammatory mediators. Therefore, it is of great value in monitoring the outcome and efficiency of orthodontic treatment. Ibuprofen a propionic acid derivative NSAID and is well absorbed orally. It is non-selective cyclooxygenase inhibitor. It has shown to have inhibitory effect on the PGE₂ levels due to its anti-inflammatory activity.⁸ However their effects on IL-1β levels in GCF is still been completely evaluated. Acetaminophen which belongs to the family of para-aminophenol, is a weak inhibitor of prostaglandin synthesis and in previous animal studies showed no effect on orthodontic tooth movement.⁹ Moreover it is known to reduce the levels of prostacyclins after systemic administration in humans.¹⁰ The orthodontist should be able to identify patients taking particular pharmaceuticals and consider any implications related to orthodontic treatment as various medications show varying effects on the rate of orthodontic tooth movement and root resorption development in human subjects.¹¹ The current study aims to determine and evaluate the effects of Ibuprofen and Acetaminophen on orthodontic pain control and GCF levels of IL-1β during initial stage of orthodontic tooth movement in human subjects. In

 

MATERIALS AND METHODOLOGY

Patients who reported to the department of orthodontics, SDM dental college and hospital, Dharwad, Karnataka for treatment were included in this study after taking approval from the ethical committee and institutional review board. The study was conducted from January 2018 to February 2019. Informed consent was obtained from all the patients included in the study. Thirty subjects (above 13 years of age; mean age:19±2years) in need of orthodontic treatment with moderate crowding in both the arches were taken for the study. The subjects were randomly divided into three equal groups. The first group was taken as the Ibuprofen group, second as the Acetaminophen group and third as the Control group.

Inclusion criteria:

1. The need for fixed orthodontic therapy.
2. No history of systemic diseases.
3. No radiographic evidence of periodontal disease.
4. No history of intake of anti-inflammatory drugs or antibiotic therapy within the past six months.

Exclusion criteria:

1. Patients who have undergone orthodontic treatment before.
2. Patients with systemic diseases.
3. Patients taking any type of medication,

Amount of dental crowding in both the arches was evaluated using Little’s Irregularity index¹² in each of the patient’s diagnostic casts which ranged from 4 to 6 (moderate irregularity) (Figure 1B). Fixed orthodontic therapy was started in all the patients included in the study after obtaining informed consent. Orthodontic preadjusted appliance (0.022’’x0.028’’ slot, MBT prescription- 3M Gemini brackets; 3M Unitek Corporation, Monrovia, California) was placed. Initial levelling and aligning was carried out using 0.014’’ Nickel Titanium (NiTi) archwire (Optima, Orthodontic Supplies Ltd, Leicestershire, UK). Lacebacks were placed using 0.010’’ ligature wire for crowding relieving. At the placement of the archwire, the subjects in the first group were given Ibuprofen, 400mg 2 times daily for 3 days. The second group received acetaminophen, 650mg 2 times daily for 3 days. The third group being control group received placebo (sugar free pills) as medication. Specific pain management instructions were given to the patients in first two groups before and immediately after initial archwire placement. The subjects were advised to rate their quality of average daily pain 24 hours after the archwire placement (P₁), 48 hours(P₂), 72 hours(P₃) and 168 hours(P₇) after the archwire placement in a pain quality rating scale evaluation sheet which was given to the patient. The patients had to rate their quality of pain on a Visual Analogue Scale (VAS) [no hurt=0, hurts worst=5], Wong Baker Faces Pain Scale, Verbal Rating Scale (0=none to 5=very severe) and six-point numerical rating scale ranging from 0 to 5.

Analysis of IL-1β Levels

GCF samples were assayed with commercially available human IL-1β ELISA (Enzyme-Linked Immunosorbent Assay) kit (Krishgen Biosystems Ltd., 3381, Paseo Drive, Brea, CA 92823, USA) to determine the concentration of IL-1β(ρg/μl).

GCF was collected at four intervals from each individual of all the three groups, amounting to a total of 120 samples.

T₀ : Before starting bonding procedure

T₁ : 24 hours after strap up

T₂ : 48 hours after strap up

T_{3 :} 168 hours after strap up

GCF was then diluted with 250μl sterile phosphate buffered saline (Ph 7.4) and stored at -80^°C until analysis.

 

 

 

 

 

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