Document Type: Original Article


1 Islamic Azad University, Garmsar branch

2 Faculty of Veterinary Medicine, Garmsar branch, Islamic Azad University,Garmsar, Iran


Objective- Evaluate analgesic effect of meloxicam and tramadol following dental extractions in cats.
Design-Experimental study
Animals-20 DSH cats who were diagnosed with 3rd or 4th stage of periodontal disease at their third mandibular premolar were entered the study in order to perform surgical dental extraction.
Procedure-A blood sample was taken prior to surgery to assess the level of cortisol and CPK. General anesthesia performed using ketamine and diazepam (IV, 8.5 mg/kg+0.2 mg/kg) and inhalation of isoflurane following intubation. 3rd mandibular premolar extracted in all of the patients using surgical procedure. The cats were randomly selected into two groups of A receiving Meloxicam (IV, 0.2 mg/kg) or B, receiving tramadol (IV, 3 mg/kg) at the time of induction of anesthesia. The analgesics were continued after the surgery for 24 hours. The score of pain were recorded using UMPS and assessment of serum level of cortisol and CPK at 2, 4 and 24 hours after the surgery performed.
Results-The highest score of pain was recorded at 4 hours after the surgery in both groups. Level of cortisol was significantly higher at 4 hours after the procedure in group B (P= 0.035). The increase in CPK was statistically significant at 2,4 and 24 hours after the surgery in group B when compared to group B (P<0.05).
Conclusion and Clinical Relevance- It is concluded that although tramadol and meloxicam are both effective in reducing pain at early hours after the surgery, meloxicam is more effective to control pain after the first few hours.


Main Subjects



Pain management is considered to be very important during anesthesia by reducing the degree and onset of pain, providing patient’s comfort and finally facilitates recovery of the patient. However, in oral surgeries, analgesia provides early return of the patient to oral feeding.1,2,3 Currently opioids and NSAIDs are mostly used to manage the pain following dental surgeries.1,4 Tramadol is a central acting synthesized opioid and demonstrates agonist action on mu receptors. Because it is considered as a non-scheduled drug in many countries, it is available in most of the situation when analgesia is required. The drug is used to manage moderate to moderately severe pain.5

Tramadol has been shown to be effective in reduction of dental pain when used alone or in combination with NSIAD.6,7,8 Meloxicam is a COX-2 selective NSAID. Evidence suggests that COX- 2 is the dominant COX isoform in the spinal cord and is associated the recognition of pain by central nervous system during inflammation. It is believed that they have fewer side effects and are less harmful to gastrointestinal mucosa.9 The drug is usually used to control moderate pain.5 It has been shown that meloxicam is effective in postoperative pain following endodontic treatments.10 Production of pain in dental surgeries is mostly due to the inflammation of the dental or associated oral tissues. Therefore, pain occurs due to inflammation and swelling of the manipulated tissues following dental surgeries that requires administration of analgesics. Thus, we hypothesized that use of NSAIDs should be superior to use of opioids in controlling pain following dental surgeries. Therefore, the objective of this study was to compare analgesic effect of meloxicam and tramadol following dental extractions in cats. Also we decided to find out if there was superiority in use of either drug in dental procedures.


Material and methods



20 cats from both sexes, weighting 3.1± 0.35 kg that were diagnosed with 3rd or 4th stage of periodontal disease in their third mandibular premolar were entered the study. Third mandibular premolar teeth were extracted using surgical technique. The cats were selected among different patients referred to the clinic for the routine dental exam. Following oral examination and dental probing, the presence of the advanced periodontal disease by presence of furcation exposure of the regarding tooth was confirmed. The animals were entered the study after the written consent was received from the owners.




A control blood sample was taken prior to surgery to assess the level of cortisol hormone and CPK enzyme. General anesthesia was performed using ketamine and diazepam (IV, 8.5 mg/kg+0.2 mg/kg) and inhalation of isoflurane in Oxygen following intubation.

The cats were randomly assigned into two groups of A receiving meloxicam (IV, 0.2 mg/kg) and B, receiving tramadol (IV, 3 mg/kg) at the time of induction of anesthesia. The analgesics were continued for 24 hours postoperatively every 8 hours.

Third mandibular premolar tooth was extracted in all of the patients by a same surgeon and using a similar procedure. In order to create an envelope mucogingival flap on buccal aspect of the tooth a No. 15 scalpel blade was used to make an incision around the gingiva. Then a periosteal elevator was

used to remove the attached gingiva from the bone and to elevate a flap. If the furcation of the roots was not evident, a high-speed turbine and the associate diamond bur were used to expose the furcation by removing alveolar bone. Next dental luxator was introduced into the periodontal space in order to luxate the tooth. Finally extraction forceps was used to extract the loosened tooth. Because the teeth were affected by stage 3 periodontal disease, therefore, tooth sectioning was not needed. The mucogingival flap was sutured to the lingual side of the extracted tooth using 4-0 polydiaxanone following alveoloplasty of the socket.

Both subjective and objective indicators of pain were used in this study including score of pain, serum level of cortisol and creatine phosphokinase enzyme (CPK). The score of pain was recorded using University of Melbourne Pain Scale (UMPS) developed by Firth and Haldane 199911 by a single trained observer in cats in both groups at 2, 4 and 24 hours following the surgery. Blood samples were taken in the EDTA tubes at 2, 4 and 24 hours after the surgery. The samples were analyzed by an Immunoanalyser (Cobas® e 411 S/N 071227, Roche Diagnostics, Mannheim, Germany). To evaluate serum levels of CPK, blood was taken in 1.5 mL microvettes and tested on an Idexx Vet Lab Station. Similar time intervals were used for the assessment of CPK enzyme levels.


Statistical analysis


Single point measurements, at any particular times, were analyzed using repeated measure ANOVA. Kruskal-Wallis test was implemented as a post hoc test using SAS. Changes in parameters over time were analyzed using GLM procedure in SAS, including repeated measures in the model. Data were presented as Mean±SEM. A value of P < 0.05 was considered significant.




All of the animals suffered from pain. There was no significant difference in score of pain between the groups (P>0.05). The highest score of pain was recorded at 4 hours after the surgery in both groups (Fig 1).

The increase in level of cortisol was occurred in all of the cats in both groups of this study. Although Mean± SD of the level of cortisol was higher in group B at 2, 4 and 24 hours after the surgery, the increase was significant only at 4 hours after the procedure in group B (P= 0.035). Also serum level of cortisol returned around its baseline values in group A 24 hours postoperatively (Fig 2). Serum level of creatine phosphokinase enzyme was increased at all measured hours after surgery in both groups.


However, the increase was statistically significant in group B at 2 (P= 0.082), 4 (P= 0.021) and 24 (P=0.010) hours after the surgery when compared to the group A. The highest Mean± SD serum level of the enzyme was recorded at 4 hours after the surgery in the group B.  Also 24 hours after the surgery, serum level of creatine phosphokinase enzyme was remained significantly higher in both groups compared to the preoperative values (Fig 3).


Pain management following dental pain prevents patient's discomfort and provides rapid recovery and early return of the patient to oral feeding. Care should be taken to select an effective analgesic regimen according to the degree of pain that the patient is supposed to suffer. Musculoskeletal and dental painis produced because of the inflammation of the tissues due to the manipulation during the procedure. Therefore, in this study we aimed to determine if there was superiority in the use of NSAID rather than opioids in controlling the pain following dental extraction in cats. Classically NSAID and opioids are used to manage the post-operative dental and oral pain.1,4 The important difference between these types of drugs is in their mechanism of action. Opioids elicit their analgesic effect by agonizing their receptors, while NSAID produce their analgesic properties by inhibiting the synthesis of prostaglandin through inhibition of the Cyclooxygenase enzymes.12,13 We observed increase in all of the indicators of pain after dental surgery that we have used in this study. The highest pain was recorded at 4 hours after postoperatively. The highest pain score was reported to be at 5 hours after the premolar dental surgery.14 We did not administer any additional rescue dose for analgesia after 24 hours following the procedure in all of the patients, since most of them were clinically appeared to be pain free. We did not observe significant different in degree of pain using the University of Melbourne Pain Scale at 2,4 and 24 hours after the procedure between the groups in this study. Serum cortisol concentration is recognized as one of the most objective criteria for pain assessment in animals and found to have direct relation with post-operative pain in dogs.15,16 Also another marker of muscle injury is creatine phosphokinase enzyme (CPK) that has been used in the assessment of pain in veterinary medicine.17 It has been shown that the serum level of the enzyme increases after the surgery and it has a positive correlation with degree of pain.18,19 The increase in serum level of cortisol explains that all of the patients in this study suffer pain, however, significant increase in the values of cortisol hormone observed at 4 hour after the surgery in the group B (P=0035). Also the serum levels of creatine phosphokinase enzyme were significantly higher in 2, 4 and 24 hours after the surgery in the group B as well. Again the highest change recorded at 4 hours after the surgery in the group B. No similar study in the field of dentistry is available regarding the increase in CPK following dental surgeries. However, dynamic correlation was found in increase of CPK, cortisol and pain following ovariohysterectomy in cats.20 Also it is shown that the increase in invasiveness of the surgery leads to increase in serum level of CPK post operatively in cruciate rupture surgeries in dogs as well as lumbar spine and disc surgeries in human.10,18-20

Maticic et al. in 2010 by comparing 2 different techniques in cranial cruciate rupture correction in dogs, indicated that the more invasive surgical technique could increase CPK either twice the less invasive one. 10

Regarding the results of the present study, meloxicam was more effective in controlling pain after early hours following the dental surgery.  NSIAD are effective in management of periodontal, postoperative dental and endodontic pain.4 Nekoofar et al in 2003, used meloxicam and reported that they were successful to control postoperative pain in patients undergone endodontic treatments using preoperative injection of meloxicam.21 Also Paracetamol which like meloxicam is believed to be a Cox-2 selective NSIAD was reported to be effective in controlling post-extraction pain of the 3rd molar teeth in human patients and also its analgesic effects are comparable to those of Ibubruphen.22,23

The results of the present study were in agreement with the results of the previous studies that compared the analgesic effects of opioids to NSAIDs in dental surgeries. Isiordia et al in 2012 during a pilot study compared the effectiveness of perioperative tramadol and meloxicam after 3rd mandibular molar extraction in human patients. The results showed that meloxicam was more effective to lower the intensity of pain than tramadol.24 Also preoperative ketorolac showed to be more effective than tramadol in controlling pain after third molar surgery. It has been indicated that the single dose of tramadol is not effective in providing analgesia following dental extractions and multiple doses are needed.2,14 Adverse effects of the NSAIDs should be considered during their use, especially when multiple doses are needed. Acute renal failure and even death have been reported after repeated doses of meloxicam in cats. However, it does not have adverse effect on glomerular filtration in short term usage.25,26 NSAIDs inhibit prostaglandin production, this means that they are most effective when used prior to production of prostaglandin due to inflammation and the subsequent pain. Therefore, in order for meloxicam to have maximum effect in managing postoperative pain after dental surgeries, it should be used prior to surgery. In conclusion both meloxicam and tramadol were effective to control post-operative pain during the first few hours after dental extraction in cats. However, meloxicam seemed to be more effective in managing pain after the first few hours and during a day after dental extraction. Preemptive analgesia is recommended when considering NSAIDs for managing pain of dental surgeries.



The authors appreciate the staff of the clinic for their help and care of animals.


Conflicts of interest


1.Becker D.E. Pain Management: Part 1: Managing Acute and Postoperative Dental Pain. Anesthesia Progress. 2010; 57(2): 67–79.

2.Ong KS, Tan JM. Preoperative intravenous tramadol versus ketorolac for preventing postoperative pain after third molar surgery. International Journal of  Oral Maxillofacial Surgery. 2004; 33(3): 274-278.

3.Mascia P, Brown BR, Friedman S. Toothache of nonodontogenic origin: a case report. Journal of Endodontics. 2003;29:608-610

4.Hargreaves K, Abbott PV. Drugs for pain management in dentistry. Australian Dental Journal Suppl 2005;50:4.

5.Becker D. E., Phero J. C. Drug therapy in dental practice: nonopioid and opioid analgesics. Anesthesia Progress. 2005;52:140–149.

6.Collins M, Young I, Sweeney P, et al. The effect of tramadol on dento-alveolar surgical pain. British Journal of  Oral Maxillofacial Surgery. 1997;35:54-58.

7.Doroschak AM, Bowles WR, Hargreaves KM. Evaluation of the combination of flurbiprofen and tramadol for management of endodontic pain. Journal of Endodontics. 1999;25:660-663.

8.Jung YS, Kim DK, Kim MK, Kim HJ, Cha IH, Lee EW. Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallelgroup study in a dental surgery pain model. Clinical Therapeutics. 2004;26:1037-1045

9.Kimmey M. B. Cardioprotective effects and gastrointestinal risks of aspirin: maintaining the delicate balance. American Journal of Medicine. 2004;117:72–78.

10.Maticic D, Stejskal M, Pecin M, Kreszinger M, Pirkic B, Vnuk D, Smolec O, Rumen- jak, V. Correlation of pain assessment parameters in dogs with cranial cruciate surgery. Veterinarski arhiv. 2010;80:597-609.

11.Firth AM, Haldane SL. Development of a scale to evaluate post operative pain. Journal of American Veterinary Medical Association. 1999, 214(5):651-9.

12.Khan AA, Dionne RA. The COX-2 inhibitors: new analgesic and anti-inflammatory drugs. Dental Clinics of North America. 2002;46(4):679-90.

13.Stein CS. The control of pain in peripheral tissue by opioids. The New England Journal of Medicine. 1995;332:1685–1690

14.Gopalraju P, Lalitha RM, Prasad K, Ranganath K. Comparative study of intravenous Tramadol versus Ketorolac for preventing postoperative pain after third molar surgery--a prospective randomized study. J of Craniomaxillofacial Surgery. 2014;42(5):629-33.

15.Feldsien JD, Wilke VL, Evans BR, Conzemius MG. (2010). Serum cortisol concentration and force plate analysis in the assessment of pain associated with sodium urate–induced acute synovitis in dogs. American Journal of Veterinary Research. 71(8): 940-945.

16.Grisneaux E, Pibarot P, Dupuis J, Blais D. Comparison of ketoprofen and carprofen administered prior to orthopedic surgery for control of postoperative pain in dogs.  Journal of American Veterinary Medical Association. 1999;215(8): 1105-10.

17.Hancock RB, Lanz OI, Warldon DR, Duncan RB, Broadstone RV, Hendrix PK. Comparison of postoperative pain following ovariohysterectomy via harmonic scalpel assisted laparoscopy versus traditional celiotomy in dogs. Veterinary Surgery. 2005; 34: 273-282.

18.Arts M, Brand R, der Kallen BV, Nijeholt GL, Peul W. Does minimally invasive lumbar disc surgery result in less muscle injury than conventional surgery? A randomized controlled trial. European Spine Journal. 2011;20(1):51–57.

19.Kawaguchi Y, Matsui H, Tsuji H. Changes in serum creatine phosphokinase MM isoenzyme after lumbar spine surgery. The Spine Journal. 1997; 22:1018–1023.

20.Tavakoli A, Shafiee B, Mohammadyar L. Correlation of post-operative pain and levels of creatin phosphokinase enzyme following ovariohysterectomy in cats. Iranian Journal of Veterinary Medicine 2016;10(1):41-46.

21.Nekoofar MH, Sadeghipanah M, Dehpour AR. Evaluation of meloxicam (A cox-2 inhibitor) for management of postoperative endodontic pain: a double-blind placebo-controlled study. Journal of Endodontics. 2003;29:634-637..Graham GG, Scott KF. Mechanism of action of paracetamol.  American Journal of Therapeutics.  2005; 12(1):46-55.

23.Barden J, Edwards JE, McQuay HJ, Andrew Moore R. Pain and analgesic response after third molar extraction and other postsurgical pain. Pain 2004; 107:86-90.

24.Isiordia-Espinoza MA, Sánchez-Prieto M, Tobías-Azúa F, Reyes-García JG.Pre-emptive analgesic effectiveness of meloxicam versus tramadol after mandibular third molar surgery: a pilot study.Journal of Oral Maxillofacial Surgery.2012;70(1):31-6.

25.Goodman LA, Brown SA, Torres BT, Reynolds LR, Budsberg SC. Effects of meloxicam on plasma iohexol clearance as a marker of glomerular filtration rate in conscious healthy cats. American Journal Veterinary Research. 2009;70(7):826-30.

26.Ingwersen W, Fox R, Cunningham G, and Winhall M. Efficacy and safety of 3 versus 5 days of meloxicam as an analgesic for feline onychectomy and sterilization. Canadian Veterinary Journal. 2012;53(3):257–264.