Efficacy of Preoperative Piroxicam, Diclofenac, Paracetamol With Tramadol and Placebo Tablets for Reduction of Postoperative Ache After the Elimination of Impacted Mandibular Third Molars: A Randomised Managed Trial



We aimed to investigate the affect of preoperative piroxicam, diclofenac, paracetamol, tramadol, and placebo tablets as measured within the time required for rescue analgesia for postoperative ache aid after the extraction of impacted mandibular third molar.

Supplies & strategies

Forty-four sufferers who wanted extraction of impacted mandibular third molar had been arbitrarily categorized into 4 teams particularly, piroxicam, diclofenac, paracetamol with tramadol, and placebo. The check drugs was given one hour preoperatively earlier than the surgical removing. The ache was assessed utilizing visible analog scale (VAS) and verbal ranking scale (VRS) scores preoperatively and on the third and 24th hours. The time required for escape analgesia was measured. 


The imply VAS and VRS scores confirmed vital variations throughout the teams after 24 hours. The imply rating was lowest for the sufferers taking piroxicam (1.30+1.95) and highest for sufferers taking tramadol + paracetamol (4.50+2.59). So far as escape analgesia is worried piroxicam group was by far superior.


The ache scores and the rescue analgesic requirement instructed that piroxicam analgesic considerably lowered ache; furthermore, it’s a secure in addition to an efficacious substitute to the standard non-steroidal anti-inflammatory medicine (NSAIDs) for mandibular third molar impactions.


Knowledge tooth impaction is a generally recognized drawback that usually calls for tooth removing. Ache, issue in opening the mouth, and edema are frequent penalties following surgical extraction of impacted third molars. This can be a results of localized inflammatory mediators, particularly cyclooxygenase (COX) and prostaglandins [1]. Good surgical strategies might assist reduce however don’t remove postoperative ache and irritation. [2]. 

The diploma of ache (gentle, reasonable, or extreme), high quality (sharp, throbbing, or uninteresting), length (transient, intermittent, or fixed), and radiation (localized or diffuse) can all change. Regardless of ache being a largely sensory expertise, it has vital cognitive and psychological results; it’s associated to or outlined by struggling. In line with The Worldwide Affiliation for the Examine of Ache (IASP), ache is “an disagreeable sensory and emotional expertise related to current or potential tissue injury or characterised by way of such hurt” [3]. 

Folks typically hyperlink dental therapies with discomfort, which makes them keep away from or postpone remedy, which makes it harder to handle [4]. The effectiveness of analgesics for acute dental ache is investigated by using a typical mannequin of extraction of an affected third molar [5]. Ache management protocols after third molar surgical procedure are crucial for offering optimum dental care. Though at current, the arsenal of native anesthetic and analgesic medicines is commonly adequate, the lack to successfully handle early postoperative ache is upsetting for each sufferers and professionals [6].

Postoperative analgesia will be delivered by means of the applying of native anesthesia or the administration of non-steroidal anti-inflammatory medicine (NSAIDs), opioids, or a mix of the 2. Preoperative use of NSAIDs probably is extra useful than postoperative use [7]; equally, opioids are additionally extra efficacious if employed previous to the surgical procedure [8-10]. The aim of administering preoperative analgesia is to keep away from or reduce ensuing ache. Pre-emptive analgesia has the impact of stopping or decreasing the formation of “reminiscence” of painful stimuli within the central nervous system. The potential for enhancing postoperative ache administration is of scientific significance [11]. The metabolites of leukotrienes, arachidonic acid, and prostaglandins are widely known to be concerned within the technique of irritation, performing as mediators and regulators of inflicting vasodilation and enhanced capillary permeability that promotes the motion of macrophages in the direction of the placement of the irritation. NSAIDs will be administered to deal with ache, trismus, in addition to edema as a result of they block the enzyme cyclooxygenase and thereby restrict the formation of prostaglandins prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) [12,13].

NSAIDs are useful for treating postoperative ache. Probably the most possible methodology of motion is inhibition of prostaglandin manufacturing [14]. Paracetamol (PCM) will not be a narcotic painkiller and has been studied for dental ache following operative procedures. Its motion mechanism will not be identified. Latest proof from animal-based and human research agrees with the idea because of the stimulation of the descending serotonergic system, PCM exerts a central analgesic impact, however its principal web site of motion is the suppression of prostaglandin synthesis. In line with biochemical investigations, cyclooxygenase-3 (COX-3) exercise that’s preferentially delicate to PCM could also be an alternate web site of motion [15,16]. Piroxicam is a non-selective cyclooxygenase inhibitor that belongs to a broad class of analgesics and NSAIDs. Piroxicam is properly absorbed half-hour after oral administration. It’s significantly useful for the remedy of many types of ache and inflammatory processes when given at a instructed dose of 20 mg as soon as a day or 10 mg twice a day [17].

Diclofenac is an NSAID that comes as potassium salt tablets for oral administration in addition to sodium salt extended-release and delayed-release tablets. Diclofenac has proven a bonus in rodent acute inflammatory fashions attributable to kaolin, carrageen, or adjuvant arthritis in pharmacologic investigations, partly resulting from suppression of the enzymatic transition of arachidonic acid into prostaglandin at extraordinarily low concentrations [18]. Diclofenac appears to have a robust inhibition impact on cyclooxygenase 1 and a couple of websites [19]. Diclofenac is swiftly plus successfully absorbed from the digestive tract, based on pharmacokinetic research. The world beneath the plasma peak concentrations and plasma concentration-time curve (AUC) is straight proportional to dosages starting from 25 to 100 mg, regardless of administration mode, and there’s no build-up with recurring therapies [20]. Tramadol is made up of two isomers which have completely different exercise spectra [21]. It stimulates each opioid and non-opioid (descending monoaminergic) pain-inhibition techniques [22]. Tramadol’s non-opioid element works by blocking norepinephrine and 5-hydroxytryptamine re-uptake and, presumably, displacing saved 5-hydroxytryptamine from nerve terminals by means of a2-agonistic and serotoninergic results [23].

The target of this randomized, placebo-controlled, double-blind examine is to see if piroxicam, diclofenac, PCM with tramadol, and placebo tablets may assist relieve postoperative ache after removing of the affected mandibular third molar.

Supplies & Strategies

This randomized managed trial was carried out at Saveetha Dental School and Hospitals in Chennai, within the Division of oral and maxillofacial surgical procedure (OMFS). In 44 sufferers, the researchers in contrast the preoperative ache aid effectiveness of oral piroxicam, diclofenac, PCM, tramadol, and placebo on ache administration following surgical removing of affected third molars. The protocol was licensed by Institutional Moral Committee, and the examine adopted the moral standards for human experimentation outlined within the Declaration of Helsinki (2000). Earlier than collaborating within the examine, all sufferers equipped written knowledgeable consent. The examine included sufferers in age between 18 to 45 years with impacted mandibular third molar.

Sufferers who had used analgesics or sedatives earlier than surgical procedure, pregnant or lactating girls, and people with systemic issues had been all excluded from the examine. Beforehand reported observations had been utilized to calculate the pattern measurement. A pattern measurement of 44 members was decided by an influence calculation of 90%. The investigator recorded the length of operation in addition to the impaction rating for every tooth (primarily based on Pell & Gregory’s classification as defined by Pederson) on the time of surgical procedure. Remedy routine allocation was randomized utilizing block randomization with a block measurement of eight. The affected person was blinded with regard to the drug being given. 

Sufferers had been positioned in 4 completely different teams: sufferers in group I obtained 20mg of piroxicam orally an hour previous to the extraction of impacted mandibular third molars, whereas sufferers in group II acquired 50mg of diclofenac sodium orally an hour previous to the extraction of impacted mandibular third molars. Sufferers in group III obtained 37.5mg tramadol + 325mg PCM orally an hour previous to the extraction of impacted mandibular third molars, whereas sufferers in group IV acquired placebo (capsule becosule) orally an hour previous to the extraction of impacted mandibular third molars.

Surgical process

Extraction of the affected third molar surgically was carried out on all of the sufferers beneath native anesthesia (lignocaine 2%, with 1:200000 epinephrine). The inferior alveolar nerve (IAN), lingual nerve, and lengthy buccal nerve had been blocked. Ward’s incision was made out of the distobuccal side of the second molar. Prolonged anteriorly and inferiorly, continued alongside the buccal side of impacted third molar and prolonged distally and laterally. A mucoperiosteal flap was mirrored to reveal the tooth. Bone was eliminated with bur beneath steady irrigation of sterile isotonic saline resolution to cut back the warmth generated, adopted by splitting and elevation of the impacted tooth. The bony margins had been filed and smoothened, and the gingival margins had been trimmed. The wound was irrigated with a sterile isotonic resolution. The flap was repositioned, and the wound was sutured with non-resorbable black silk suture materials. A stress pack was given to achieve hemostasis. Postoperatively, for all sufferers, amoxicillin 500mg thrice each day was given. The sutures had been eliminated for all sufferers on the seventh postoperative day.

Rescue medicine

As a rescue medicine, aceclofenac (100mg) + PCM (325mg) mixture was given to sufferers who didn’t attain adequate ache aid. Sufferers who had consumed rescue medicine earlier than three hours had been excluded from the ultimate evaluation.

Efficacy evaluation

Visible Analogue Scale (VAS)

Sufferers had to make use of the VAS scale with readings from 0 to 10 with a gradation of 1. The ache depth was recorded one hour earlier than surgical procedure, instantly earlier than taking a pre-emptive analgesic, then within the third and twenty fourth hour after the surgical procedure. Anchor factors had been 0, which indicated no ache, and 10, which indicated extreme ache. 

Verbal Score Scale (VRS)

Sufferers had been requested to make use of a VRS scale with readings as a) no ache, b) gentle, c) reasonable, and d) extreme ache.

Time to remedication

The time to remedication is the time between the termination of surgical procedure and the affected person’s want for rescue medicine. The time {that a} participant acquired rescue remedy (aceclofenac + PCM) was recorded.

Descriptive and inferential statistics had been employed to execute the statistical evaluation, together with the Kruskal-Wallis check, Mann-Whitney check, and Chi-square check. The software program used within the examine was SPSS model 27.0 (IBM Inc., Armonk, New York), and the importance degree was analyzed as p<0.05.


All the sufferers adopted the analysis protocol, endured the surgical procedures properly, and returned for follow-up appointments. Forty-four sufferers who met our eligibility standards agreed to participate on this examine and underwent surgical removing of affected third molars. Out of those 44 sufferers, one affected person was withdrawn due to an opposed drug response, and two sufferers needed to be excluded from the evaluation due to consumption of rescue medicine earlier than the third-hour analysis of ache.


Out of 44 sufferers on this examine, 10 sufferers within the diclofenac group had eight males and two females. Out of 10 sufferers who had been within the piroxicam group, seven had been males and three had been females. There was an equal distribution of women and men in PCM with the tramadol group. There have been 5 males and 6 females within the placebo group of 11 sufferers. There was no substantial distinction by way of affected person distribution primarily based on impaction issue (Desk 1).

  Group N Imply Std. Dev Min Max P-value
Issue degree Diclofenac 10 5 0.943 4 6 0.32
Piroxicam 10 4.7 1.418 3 7
Placebo 11 4.09 1.136 3 6
Tramadol + paracetamol 10 4.7 1.252 3 6
Complete 41 4.61 1.202 3 7

Ache scores

Desk 2 depicts the imply VAS scores between teams over time. The imply VAS rating didn’t present any substantial distinction between the teams earlier than the surgical process and three hours postoperatively (p>0.05).

VAS Drug N Imply Std. Dev Min Max P-value
Earlier than Diclofenac 10 1.7 1.83 0 6 0.763
Piroxicam 10 2.6 2.37 0 8
Placebo 11 2 2.05 0 6
Tramadol + paracetamol 10 1.7 2.62 0 5
Complete 41 2 1.92 0 8
After 3 hours Diclofenac 10 3.9 3.18 1 8 0.435
Piroxicam 10 2.4 1.51 0 5
Placebo 11 4.09 2.26 1 8
Tramadol + paracetamol 10 2.7 2.31 0 8
Complete 41 3.29 2.41 0 8
After 24 hours Diclofenac 10 3.4 3.13 0 8 0.02
Piroxicam 10 1.3 1.95 0 6
Placebo 11 2.36 1.12 1 5
Tramadol + paracetamol 10 4.5 2.59 1 8
Complete 41 2.88 2.51 0 8
ESC ANG (hours) Diclofenac 5 8 8.97 3 24 0.001
Piroxicam 1 5 5 5
Placebo 11 2 0 2 2
Tramadol + paracetamol 4 4.88 1.44 3 6
Complete 21 4.12 4.77 2 24

The imply VAS rating confirmed a major distinction throughout the teams after 24 hours. The imply rating was lowest for the sufferers taking piroxicam (1.30+1.95) and highest for sufferers taking tramadol + PCM (4.50+2.59). The distinction throughout the teams at 24 hours was statistically vital (p<0.05).

Desk 3 depicts Mann-Whitney check to check the pairwise imply and demonstrates no notable distinction between diclofenac vs. piroxicam, diclofenac vs. placebo, diclofenac vs. tramadol + PCM (p>0.05) after 24 hours however there’s a vital distinction between Piroxicam vs. placebo, piroxicam vs. tramadol + PCM, placebo vs. tramadol + PCM (p<0.05).

  Group P-value
VAS after 24Hrs Diclofenac vs. piroxicam 0.074
Diclofenac vs. placebo 0.717
Diclofenac vs. tramadol + paracetamol 0.378
Piroxicam vs. placebo 0.036
Piroxicam vs. tramadol + paracetamol 0.005
Placebo vs. tramadol + paracetamol 0.049
ESC ANG Diclofenac vs. piroxicam 0.546
Diclofenac vs. placebo <0.001
Diclofenac vs. tramadol + paracetamol 0.71
Piroxicam vs. placebo 0.001
Piroxicam vs. tramadol + paracetamol 0.999
Placebo vs. tramadol + paracetamol 0.001

Desk 4 exhibits the proportion of sufferers in every group that require rescue analgesia. 5 sufferers within the diclofenac group took rescue analgesia, one within the piroxicam group, and 4 within the PCM with tramadol group.

Group ESC ANG wanted P-value
No Sure Complete
N % N % N %
Diclofenac 5 50 5 50 10 100 0.001*
Piroxicam 9 90 1 10 11 100
Placebo 0 0 11 100 11 100
Tramadol + paracetamol 6 60 4 40 11 100
Complete 20 48.8 21 51.2 43 100  

Desk 5 depicts Chi-test to check the proportions of VRS rating between teams, which exhibits no vital distinction between teams earlier than surgical procedure and three hours after surgical procedure (p>0.05). Nevertheless, there was a substantial distinction between the teams after 24 hours (p< 0.05).

Verbal response scale Drug Group Complete P-value*
Diclofenac Piroxicam Placebo Tramadol+ paracetamol
N % N % N % N % N %
Earlier than surgical procedure No 2 20 1 10 4 36.4 2 20 9 22 0.962
Gentle 7 70 7 70 6 54.5 7 70 27 65.9
Reasonable 1 10 1 10 1 9.1 1 10 4 9.8
Extreme 0 0 1 10 0 0 0 0 1 2.4
Complete 10 100 10 100 11 100 10 100 41 100  
 After 3 hours No 0 0 1 10 0 0 2 20 3 7.3 0.389
Gentle 6 60 7 70 6 54.5 7 70 26 63.4
Reasonable 2 20 2 20 4 36.4 0 0 8 19.5
Extreme 2 20 0 0 1 9.1 1 10 4 9.8
Complete 10 100 10 100 11 100 10 100 41 100  
After 24 hours No 2 20 5 50 0 0 0 0 7 17.1 0.018
Gentle 5 50 4 40 10 90.9 5 50 24 58.5
Reasonable 1 10 1 10 1 9.1 3 30 6 14.6
Extreme 2 20 0 0 0 0 2 20 4 9.8
Complete 10 100 10 100 11 100 10 100 41 100  


Extraction of the affected mandibular third molars surgically is without doubt one of the commonest dentoalveolar interventions in oral and maxillofacial surgical procedure, which is linked with variable levels of postoperative discomfort. The most typical postoperative complaints are ache, trismus, and edema; therefore it could have an effect on the standard of lifetime of a affected person within the days post-surgery [24].

Acute tissue harm attributable to surgical operations ends in activation of peripheral nociceptors, which has an affect on the central nervous system. The ensuing main and secondary hyperalgesia finest exemplifies the intensive affect of native web site accidents on the nervous system [25]. Major hyperalgesia, characterised by an enhanced sensitivity towards thermal and mechanical stimuli [26], happens because of the sensitization of peripheral cutaneous receptors by inflammatory mediators corresponding to prostaglandins [27]. Secondary hyperalgesia is because of a rise in sensitivity in the direction of mechanical stimulus in areas surrounding the positioning of harm [3]. Secondary hyperalgesia is attributable to central sensitization of trigeminal nucleus neurons together with the dorsal horn and based on new knowledge, supra-spinal buildings, together with the rostral ventral medulla, play a major function within the institution and upkeep of sympathetic activation and secondary hyperalgesia [28]. 

Latest literature means that prostaglandins and cyclooxygenases, along with their roles within the peripheral nervous system, even have essential roles within the central nervous system [29]. Because of this, main hyperalgesia primarily entails the peripheral processes, which might lead rise to secondary hyperalgesia primarily utilizing central mechanisms and trigger ache postoperatively. In most circumstances, as a result of postoperative ache is a predicted occasion, actions must be undertaken to cut back affected person discomfort related to surgical operations.

Prostaglandins are essential molecules concerned in peripheral nociceptors sensitization, which results in main and secondary hyperalgesia. Prostaglandins are produced by activating phospholipase A2 in broken tissue, which leads to the creation of arachidonic acid from membrane phospholipids. After that, cyclooxygenase (COX)-dependent mechanisms convert arachidonic acid to completely different prostaglandins. Prostaglandin D2 (PGD2), PGE2, thromboxane A2 (TxA2), PGI2 (prostacyclin), and prostaglandin F2 (PGF2) alpha are the 5 main prostanoids within the prostaglandin household. These prostaglandins then affect the physique by attaching to sure G-linked receptor proteins. The prostanoid PGE2 is very necessary in acute irritation, and its ranges are linked to the diploma of ache following knowledge tooth extraction [30]. 

As prostaglandins usually are not current in massive portions in regular tissues to be lively and should first be generated, they are not concerned within the first response to ache that results in tissue injury [31]. After tissue harm, prostaglandins are quickly produced and emerge in excessive portions one hour later. COX-1 is present in a wide range of organs and is concerned in gastric mucosa safety, platelet aggregation, and renal blood circulation management [32]. COX-1 is typically known as the constitutive COX enzyme as a result of it’s present in regular tissues. COX-2 is current in lots of regular tissues, together with the glomerulus, kidney, spinal twine, brainstem, and mind; nonetheless, COX-2 expression is elevated in pathological circumstances like power inflammatory illnesses; therefore additionally it is often known as the inducible COX enzyme [33].

The thought of utilizing NSAIDs to alleviate postoperative ache, both as a single remedy or mixed with different medicines, is getting widespread as extra is revealed about their mechanisms of motion [34]. NSAIDs inhibit prostaglandin formation by COX-1 and COX-2 pathways – inhibition of COX-1 could possibly be implicated with the formation of widespread NSAID negative effects, whereas blockage of COX-2 results in analgesia [35]. There are a number of strategies for coping with ache. The revelation that central sensitization of intrinsic dorsal horn neurons in animal ache fashions is perhaps lowered if medicine had been administered earlier than the harm occurred highlighted an necessary potential improvement within the remedy of ache following surgical procedures [3,36]. The discount in modifications in these neurons discovered when the medicine are administered previous to the injury provides rise to the thought of pre-emptive analgesia [37]. In line with scientific analysis, an analgesic given pre-surgery appears to have a greater end result than the identical drug given post-surgery. The analysis signifies that there was no vital variation within the third hour after surgical procedure, though the piroxicam group was superior on the twenty fourth hour.

The intention of this examine is to check the impact of preoperative analgesia within the 4 teams as measured within the time required for rescue analgesia for the aid of postoperative ache. Treatment with the aceclofenac-PCM mixture was allowed to the affected person on the prevalence of ache postoperatively earlier than the scheduled dosage of the check drug. The piroxicam group consumed much less rescue analgesia than the opposite teams. In a examine by Ong et al., prophylactic intravenous ketorolac 30 mg was proven to be extra useful than tramadol 50 mg in stopping postoperative tooth discomfort [38]. One other examine discovered that people who acquired preoperative meloxicam 15 mg lowered ache depth and total analgesic consumption in comparison with 50 mg tramadol preoperatively [39].

Tramadol is a wonderful postoperative painkiller; nonetheless, the appreciable opposed results of vomiting and nausea restrict its widespread use [40]. Since 37.5mg of tramadol was utilized in our trial, no destructive results had been seen. Rousan et al. demonstrated that preoperative diclofenac sodium medicine supplied efficient alleviation from gentle to reasonable ache following knowledge tooth surgical procedure as in comparison with postoperative dosing [41]. Tuzuner et al. investigated the postoperative pain-relieving results of prophylactic intravenous PCM (perfalgan) and in people present process impacted knowledge tooth surgical procedure, intramuscular diclofenac sodium and intravenous lornoxicam had been used. In line with the findings, preoperative diclofenac, lornoxicam, and intravenous PCM successfully lowered postoperative flurbiprofen consumption and ache severity [42].

That is the primary of its sort of examine to check piroxicam, diclofenac, and PCM to tramadol earlier than surgical procedure. Piroxicam, a non-selective cyclooxygenase inhibitor, is without doubt one of the NSAIDs which is useful for the remedy of varied sorts of ache and inflammatory processes when taken at a instructed dose of 20 mg as soon as a day or 10 mg twice a day [17]. Kohli et al. in contrast ache medicine with 400 mg of ibuprofen or placebo, trying to include 20 mg of piroxicam resulted in reporting a lot much less ache. Piroxicam has a major half-life and consequently a extra distinguished impact than diclofenac and PCM mixed with tramadol. It’s potential that utilizing piroxicam as a preoperative analgesic consequence in better postoperative ache aid [43].


Ache management is probably the most crucial side to be thought-about following impacted tooth surgical removing for efficient perioperative ache administration. On this examine, piroxicam 20mg given one hour preoperatively considerably lowered rescue analgesia requirement. This examine provides to the rising data of the usage of piroxicam as preoperative analgesia in perioperative ache administration throughout third molar surgical procedure. Piroxicam, a non-selective cyclooxygenase inhibitor, is without doubt one of the NSAIDs which is useful for the remedy of varied sorts of ache and inflammatory processes when taken at a instructed dose of 20 mg as soon as a day or in a divided dose.


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