The Effect of Tramadol on Blood Glucose Levels in Rats

Hacer Kara, Ayse Karci, Mukaddes Gümüştekin, Murat Örmen, Aydin Taşdöğen, Zahide Elar

Department of Anesthesiology and Reanimation, Dokuz Eylül University Medical School, ?zmir, Turkey.
Department of Biochemistry, Dokuz Eylül University Medical School, ?zmir, Turkey.
Department of Pharmacology, Dokuz Eylül University Medical School, ?zmir, Turkey.

DOI: 10.4236/ojanes.2013.31006                

Abstract

The Background: Tramadol, is a central acting analgesic that possesses weak affinity for the μ-opioid receptor and modifies transmission of nociceptive impulses through inhibition of monoamine reuptake. This study was designed to determine the effect of tramadol on blood glucose levels and also to investigate whether or not alpha-2 adrenergic receptors were responsible for this effect. Methods: Twenty-five Wistar male rats were assigned to four groups to receive: Group I: saline; Group II: tramadol (1 mg·kg^-1); Group III and Group IV: pretreatment with a₂-receptor antagonist drugs yohimbine (1 mg·kg^-1) or idazoxan (1 mg·kg^-1), 30 min before administration of tramadol (1 mg·kg^-1). Samples for plasma glucose measurement were withdrawn at 0, 30, 60, 90 and 120 minutes of the experiment. Results: A significant rise in blood glucose levels was observed following administration of i.v. tramadol. Pretreatment with both yohimbine and idazoxan (1 mg·kg^-1) significantly attenuated tramadol-induced hyperglycemia. Conclusion: The results of the study indicate that, tramadol administered at an analgesic dose of 1 mg·kg^-1 produces hyperglycemia in diethyl ether anesthetized rats. Reversal of this effect with a₂-adrenoceptor blocking agents suggests that monoaminergic pathways which contribute to the analgesic action of tramadol, may have a role in the hyperglycemic action of the drug.

Keywords

Hyperglycemia; Tramadol; a₂Antagonist; Antinociceptive Effect; Yohimbine; Idazoxan; Rat

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	E. A. Shipton, “Tramadol—Present and Future,” Anaesthesia and Intensive Care, Vol. 28, No. 4, 2000, pp. 363 374.
[2]	D. J. R. Duthie, “Remifentanil and Tramadol,” British Journal of Anaesthesia, Vol. 81, No. 1, 1998, pp. 51-57. doi:10.1093/bja/81.1.51
[3]	J. A. Desmeules, V. Piguet, L. Collart and P. Dayer, “Contribution of Monoaminergic Modulation to the Analgesic Effect of Tramadol,” British Journal of Clinical Pharmacology, Vol. 41, No. 1, 1996, pp. 7-12. doi:10.1111/j.1365-2125.1996.tb00152.x
[4]	V. Kayser, G. Guilbaud and J. M. Besson, “Potent Antinociceptive Effects of Clonidine Systemically Administered in an Experimental Model of Clinical Pain, the Arthritic Rat,” Brain Research, Vol. 593, No. 1, 1992, pp. 7-13. doi:10.1016/0006-8993(92)91255-D
[5]	B. Driessen and W. Reimann, “Interaction of the Central Analgesic, Tramadol, with the Uptake and Release of 5-Hydroxytryptamine in the Rat Brain in Vitro,” British Journal of Pharmacology, Vol. 105, No. 1, 1992, pp. 147 151. doi:10.1111/j.1476-5381.1992.tb14226.x
[6]	B. C. Bloor, M. Maze and I. Segal, “Interaction between Adrenergic and Opioid Pathways,” In: F. G. Estafanous, Ed., Opioids in Anesthesia II, Reed Publishing, Stoneham, 1991, pp. 35-45.
[7]	K. A. Eggers and I. Power, “Tramadol,” British Journal of Anaesthesia, Vol. 74, No. 3, 1995, pp. 247-249. doi:10.1093/bja/74.3.247
[8]	R. B. Raffa, E. Friderichs, W. Reimann, R. P. Shank, E. E. Codd and J. L. Vaught, “Opioid and Nonopioid Components Independently Contribute to the Mechanism of Action of Tramadol, an ‘Atypical’ Opioid Analgesic,” Jour nal of Pharmacology and Experimental Therapeutics, Vol. 260, No. 1, 1992, pp. 275-285.
[9]	J. Moratinos, B. Olmedilla, I. de Pablos and M. D. Vi gueras, “Alpha-Adrenoceptor Involvement in Catechola mine-Induced Hyperglycaemia in Conscious Fasted Rabbits,” British Journal of Pharmacology, Vol. 89, No. 1, 1986, pp. 55-66. doi:10.1111/j.1476-5381.1986.tb11120.x
[10]	I. Angel and S. Z. Langer, “Adrenergic-Induced Hyperglycemia in Anaesthetized Rats: Involvement of Peripheral Alpha 2-Adrenoceptors,” European Journal of Pharmacology, Vol. 154, No. 2, 1988, pp. 191-196. doi:10.1016/0014-2999(88)90097-0
[11]	I. Angel, R. Niddam and S. Z. Langer, “Involvement of Alpha-2 Adrenergic Receptor Subtypes in Hyperglycemia,” Journal of Pharmacology and Experimental Therapeutics, Vol. 254, No. 3, 1990, pp. 877-882.
[12]	G. W. John, J. C. Doxey, D. S. Walter and J. L. Reid, “The Role of Alpha and Beta-Adrenoceptor Subtypes in Mediating the Effects of Catecholamines on Fasting Glucose and Insulin Concentrations in the Rat,” British Journal of Pharmacology, Vol. 100, No. 4, 1990, pp. 699-704. doi:10.1111/j.1476-5381.1990.tb14078.x
[13]	R. Niddam, I. Angel, S. Bidet and S. Z. Langer, “Pharmacological Characterization of Alpha-2 Adrenergic Receptor Subtype Involved in the Release of Insulin from Isolated Rat Pancreatic Islets,” Journal of Pharmacology and Experimental Therapeutics, Vol. 254, No. 3, 1990, pp. 883-887.
[14]	K. Budd, “The Role of Tramadol in Acute Pain Management,” Acute Pain, Vol. 2, No. 4, 1999, pp. 189-196. doi:10.1016/S1366-0071(99)80019-9
[15]	M. D. Vickers, D. O’Flaherty, S. M. Szekely, M. Read and J. Yoshizumi, “Tramadol: Pain Relief by an Opioid without Depression of Respiration,” Anaesthesia, Vol. 47, No. 4, 1992, pp. 291-296. doi:10.1111/j.1365-2044.1992.tb02166.x
[16]	J. T. Cheng, I. M. Liu, T. C. Chi, T. F. Tzeng, F. H. Lu and C. J. Chang, “Plasma Glucose-Lowering Effect of Tramadol in Streptozotocin-?nduced Diabetic Rats,” Dia betes, Vol. 50, No. 12, 2001, pp. 2815-2821. doi:10.2337/diabetes.50.12.2815
[17]	H. A. Abouazra and S. I. Sharif, “Hyperglycaemia: A Morphine-Like Effect Produced by Naloxone,” Clinical and Experimental Pharmacology and Physiology Vol. 28, No. 4, 2001, pp. 300-305. doi:10.1046/j.1440-1681.2001.03442.x