Radiographic and histopathologic evaluation of inhibitory effects of Tramadol and Metamizol on experimental bone defect healing in rabbit tibia

Document Type : Research Paper

Authors

1 Associate Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Associate Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Assistant Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

4 DVSc Graduated of Veterinary Surgery, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Nonsteroidal anti-inflammatories and opioids are of drugs that have been widely used to manage the pain after orthopedic surgery in human and animals. The purpose of this study was to compare the inhibitory effects of metamizol and tramadol on bone defect healing in rabbit tibia. In this study, thirty male New Zealand white rabbits were divided into two groups. A 5 mm in diameter circular defect was created on the medial surface of the tibial metaphyseal region of the right foot of each rabbit. Respectively, in metamizole and tramadol groups, metamizole, 5 mg / kg and tramadol 4 mg/ kg were subcutaneously administrated In a 5-day course of treatment every 12 hours and then every 24 hours during a three-day. Defect healing was assessed by obtaining radiographs on 0, 7, 14, 21, 28, 35, 42 days after surgery. Also, histopathologic evaluation was done at 7, 21 and 45 days using Goldner’s trichrome staining. It also represents a faster start filling defect in the histopathological study, following administration of tramadol compared with metamizole. Also, at the end of the study, tramadol achived more filling defect points compared with metamizole. The results of this study showed that the beginning of the process of callus formation in metamizol was later than tramadol, so there was a significant difference between groups, in the formation of callus so that in the radiographs taken on 14, 28 and 35 days. The results of this study showed that in comparison with Tramadol, metamizol has more effects in slowing bone repair.

Keywords

Main Subjects


Altman, R.D.; Latta, L.L.; Keer, R.; Renfree, K.; Hornicek,  F.J. and Banovac, K. (1995). Effect of nonsteroidal antiinflammatory drugs on fracture healing: a laboratory study in rats. Journal of Orthopaedic Trauma, 9(5): 392-400.

Alves, I.P.G.; Nicacio, G.M.; Diniz, M.S.; Rocha, T.L.A.; Kanashiro, G.P. and Cassu, R.N. (2014). Analgesic comparison of systemic lidocaine, morphine or lidocaine plus morphine infusion in dogs undergoing fracture repair. Acta Cirurgica Brasileira, 29(4): 245-251.
Bagher, Z.; Rajaei, F. and Shokrgozar, M. (2012). Comparative study of bone repair using porous hydroxyapatite/β-tricalcium phosphate and xenograft scaffold in rabbits with tibia defect. Iranian Biomedical Journal, 16(1): 18-24.
Ballantyne, J. (1998). Tramadol: Its role in acute pain management. Acute Pain, 1 (2): 5-6.
Barry, S. (2010). Non-steroidal anti-inflammatory drugs inhibit bone healing, A review. Veterinary and Comparative Orthopaedics and Traumatology, 23(6): 385-392.
Baumgartner, C.M.; Koenighaus, H.; Ebner, J.K.; Henke, J.; Schuster, T. and Erhardt, W.D. (2009). Cardiovascular effects of dipyrone and propofol on hemodynamic function in rabbits. American Journal of Veterinary Research, 70(11): 1407-1415.
Beck, A.; Krischak, G.; Sorg, T.; Augat, P.; Farker, K.; Merkel, U. et al. (2003). Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing. Archives of Orthopaedic and Trauma Surgery, 123(7): 327-332.
Bhattacharyya, T.; Levin, R.; Vrahas, M.S. and Solomon, D.H. (2005). Nonsteroidal antiinflammatory drugs and nonunion of humeral shaft fractures. Arthritis and Rheumatism, 53(3): 364-367.
Bigham-Sadegh, A.; Karimi, I.; Alebouye, M.; Shafie-Sarvestani, Z. and Oryan, A. (2013). Evaluation of bone healing in canine tibial defects filled with cortical autograft, commercial-DBM, calf fetal DBM, omentum and omentum-calf fetal DBM. Journal of Veterinary Science, 14(3): 337-343.
Brinker, M.R.; O’Connor, D.P.; Monla, Y.T. and Earthman, T.P. (2007). Metabolic and endocrine abnormalities in patients with nonunions. Journal of Orthopaedic Trauma, 21(8): 557-570.
Budd, K. and Langford, R. (1999). Tramadol revisited (Editorial). British Journal of Anaesthesia, 82 (4): 493-495.
Burd, T.A.; Hughes, M.S. and Anglen, J.O. (2013). Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion. Journal of Bone Joint and Surgery (British), 85(5): 700-705.
Chrastil, J.; Sampson, C.; Jones, K.B. and Higgins, T.F. (2013). Postoperative opioid administration inhibits bone healing in an animal model. Clinical Orthopaedics and Related Research, 471(12): 4076-4081.
Clarke, K.W.; Trimb, C.M. and HallL, W. (2014).Veterinary Anaesthesia. 11th ed. Saunders, London, pp: 101-133.
Cottrell, J.A.; Meyenhofer, M.; Medicherla, S.; Higgins, L. and O’Connor, J.P. (2009). Analgesic effects of p38 kinase inhibitor treatment on bone fracture healing. Pain, 142(1): 116-126.
Delgado-Ruiz, R.A.; Calvo-Guirado, J.L.; Abboud, M.; Ramirez-Fernández, M.P.; Maté-Sánchez, J.E.; Negri, B. et al. (2014). Porous titanium granules in critical size defects of rabbit tibia with or without membranes. International Journal of Oral Sciences, 6(2):105-110.
Dimmen, S.; Nordsletten, L. and Madsen, J.E. (2009). Parecoxib and indomethacin delay early fracture healing: a study in rats. Clinical Orthopaedics and Related Research, 467(8): 1992-1999.
Elves, M.W.; Bayley, I. and Roylance, P.J. (1982). The effect of indomethacin upon experimental fractures in the rat. Acta Orthopaedica, Scandinavica, 53(1): 35-41.
Engesater, L.B.; Sudmann, B. and Sudmann, E. (1992). Fracture healing in rats inhibited by locally administered indomethacin. Acta Orthopaedica, Scandinavica, 63(3): 330-333.

Gali, J.C.; Sansanovicz, D.; Ventin, F.C.; Paes, R.H.; Quevedo, F.C. and Caetano E.B. (2014). Dipyrone has no effects on bone healing of tibial fractures in rats. Acta Ortopedica Brasileira, 22(4): 210-213.

Gerstenfeld, L.; Al-Ghawas, M.; Alkhiary, Y.; Cullinane, D.; Krall, E.; Fitch, J. et al. (2007). selective and nonselective cyclooxygenase-2 inhibitors and experimental fracture-healing reversibility of effects after short-term treatment. Journal of Bone and Joint Surgery (American), 89(1):114-125.
Grond, S. and Sablotzki, A. (2004). Clinical pharmacology of tramadol. Clinical Pharmacokinetics, 43(13): 879-923.
Gurgel, B.C.D.V.; Ribeiro, F.V.; Silva, M.A.D.D.; Nociti Júnior, F.H.; Sallum, A.W.; Sallum, E.A. et al. (2005). Selective COX-2 inhibitor reduces bone healing in bone defects. Brazilian Oral Research, 19(4): 312-316.
Halfpenny, D.M.; Callado, L.F.; Hopwood, S.E.; Bamigbade, T.A.; Langford, R.M. and Stamford, J.A. (1999). Effect of tramadol stereoisomers on norepinephrine efflux and uptake in the rat locus coeruleus measured by real time voltammetry. British Journal of Anaesthesia, 83(6): 909-915.
Herbenick, M.A.; Sprott, D.; Stills, H. and Lawless, M. (2008). Effects of a cyclooxygenase 2 inhibitor on fracture healing in a rat model. American Journal of Orthopaedics, 37(7): E133-E137.
Hogevold, H.E.; Grogaard, B. and Reikeraas, O. (1992). Effect of short-term treatment with corticosteroids and indomethacin on bone healing: a mechanical study of osteotomies in rats. Acta Orthopaedica Scandinavica, 63(6): 607-611.
Huo, M.H.; Troiano, N.W.; Pelker, R.R.; Gundberg, C.M. and Friedlaender, G.E. (1991). The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. Journal of Orthopaedic Research, 9(3): 383-390.
Imagawa, V.H.; Fantoni, D.T.; Tatarunas, A.C.; Mastrocinque, S.; Almeida, T.F.; Ferreira, F. and Posso, I.P. (2011). The use of different doses of metamizol for post-operative analgesia in dogs. Veterinary Anaesthesia and Analgesia, 38(4): 385-393.
Jakob, M.; Demarteau, O.; Suetterlin, R.; Heberer, M. and Martin, I. (2004). Chondrogenesis of expanded adult human articular chondrocytes is enhanced by specific prostaglandins. Rheumatology (Oxford), 43: 852-857.
Jasiecka, A.; Maslanka, T. and Jaroszewski, J.J. (2014). Pharmacological characteristics of metamizole. Polish Journal of Veterinary Sciences, 17(1): 207-214.
Krischak, G.D.; Augat, P.; Sorg, T.; Blakytny, R.; Kinzl, L.; Claes, L. and Beck, A. (2007). Effects of diclofenac on periosteal callus maturation in osteotomy healing in an animal model. Archives of Orthopaedic and Trauma Surgery, 127: 3-9.
KuKanich, B.; Bidgood, T. and Knesl, O. (2012). Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs. Veterinary Anaesthesia and Analgesia, 39(1): 69-90.
Landwehr, S.; Kiencke, P.; Giesecke, T.; Eggert, D.; Thumann, G. and Kampe, S. (2005). A comparison between IV paracetamol and IV metamizole for postoperative analgesia after retinal surgery. Current Medical Research and Opinion, 21(10): 1569-1575.
Lee, S.C. and Han, T.H. (2001). Clinical efficacy and safety of slow-release tramadol for chronic osteoarthritis in an outpatient pain clinic. European Journa lof Pain, 5(1): 131-134.
Marsh, D.R. and Li, G. (1999). The biology of fracture healing: optimising outcome. British Medical Bulletin, 55(4):856-869.
Oh, N.; Sunaga, T.; Yamazaki, H.; Hosoya, K.; Takagi, S. and Okumura, M. (2013). Limited inhibitory effects of non-steroidal anti-inflammatory drugs on in vitro osteogenic differentiation in canine cells. Japanese Journal of Veterinary Research, 61(3):97-107.
Pape, H.C.; Marcucio, R.; Humphrey, C.; Colnot, C.; Knobe M. and Harvey E.J. (2010). Trauma-induced inflammation and fracture healing. Journal of Orthopaedic Trauma, 24(9): 522-525.
Peters, A.; Ignatius, A.; Pohlemann, T.; Claes, L. and Menger, M.D. (2011). Small animal bone healing models: Standards, tips, and pitfalls results of a consensus meeting Bone, 49(4): 591-599.
Ruiz-Suarez, M. and Barber, F.A. (2008). Postoperative pain control after shoulder arthroscopy. Orthopedics, 31(11), 1130.
Shipton, E.A.; Roelofse, J.A. and Blignaut, R.J. (2003). An evaluation of analgesic efficacy and clinical acceptability of intravenous tramadol as an adjunct to propofol sedation for third molar surgery. Anesthesia Progress, 2003; 50(3): 121-128.
Simon, AM.; Manigrasso, M.B. and O'Connor, J.P. (2002). Cyclo-oxygenase 2 function is essential for bone fracture healing. Journal of Bone Mineral Research,17(6): 963-976.
Spiro, A.S.; Timo Beil, F.; Baranowsky, A.; Barvencik, F.; Schilling, A.F.; Nguyen, K. et al. (2010). BMP-7- induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice. Journal of Orthopedic Research, 28: 785-791.
Tranquilli, W.J.; Thurmon, J.C. and Grimm, K.A. (2007). Lumb and Jones’ Veterinary Anesthesia and Analgesia. 4th ed. Blackwell Publishing, pp: 765-785.
Urrutia, J.; Mardones, R. and Quezada, F. (2007). The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Journal of Neurosurgery: Spine, 7(6): 631-636.
Wehner, T.; Wolfram, U.; Henzler, T.; Niemeyer, F.; Claes, L. and Simon, U. (2010). Internal forces and moments in the femur of the rat during gait. Journal of Biomechanics, 43: 2473-2479.
Welting, T.J.M.; Caron, M.M.J.; Emans, P.J.; Janssen, M.P.F.; Sanen, K.; Coolsen, M.M.E. et al. (2011). Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification. European Cells and Materials, 22: 420-437.