Alterations in aminergic system of rat brain by the opioid analgesic tramadol in the absence of pain-induction

Authors

  • Sahitya C. Panadanabiona Department of Biology, Arkansas Biosciences Institute, Jonesboro, Arkansas, USA

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20175161

Keywords:

Biogenic amines, Non-nociception, Rat brain areas, Tramadol

Abstract

Background: Tramadol is an opioid analgesic used for treating moderate to severe pain. No research is available on pharmacology of tramadol without induction of pain. This study examines the effect of administration of tramadol on the levels of biogenic amines and their metabolites in the brain areas of male adult Wistar rats, without inducing pain.

Methods: Tramadol was injected subcutaneously at 0, 24, and 48 hours, and changes in the levels of epinephrine (EP), norepinephrine (NE), dopamine (DA) and serotonin (5-HT), 5-hydroxyindoleacetic acid (HIAA) and homovanillic acid (HVA) were examined in cerebral cortex, cerebellum, pons-medulla, hippocampus and thalamus. The changes were recorded in the select brain areas at 3, 6, 12, 24 hours after the first injection, as well as at 24 hours after the second and third injections, respectively.

Results: Administration of tramadol at 0 hours elevated the levels of DA, 5-HT and HVA in all brain areas. Changes in levels of EP, NE, and HIAA varied across the four brain areas surveyed. All parameters showed maximal changes at 3 or 6 hours following the first administration at 0 hours. For the second and third doses of tramadol at 24 and 48 hours respectively, the parameters showed variations at 48 and 72 hours that generally fluctuated around the control.

Conclusions: The results indicate differential tissue responses to administered tramadol in different areas of the brain. The results suggest that the alterations in biogenic amines for the administration of tramadol are similar under both pain and no-pain conditions.

References

Fürst S. Transmitters involved in antinociception in the spinal cord. Brain Res Bull. 1999;48(2):129-41.

Leknes S, Tracey I. A common neurobiology for pain and pleasure. Nat Rev Neurosci. 2008;9(4):314-20.

Gutstein HB, Akil H. Opioid analgesics. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 2001:569.

Fries DS. Opioid analgesics. In: Foye's Principles of Medicinal Chemistry. Philadelphia: Williams and Wilkins Lippincott; 2002:453.

Schäfer M. Peripheral opioid analgesia: from experimental to clinical studies. Current Opinion in Anaesthesiology. 1999;12(1):603-7.

Stein C. Opioid receptors on peripheral sensory neurons. In: Immune Mechanisms of Pain and Analgesia. Georgetown: Eurekah.com/Landes Bioscience; 2001:69.

Hummel T, Roscher S, Pauli E, Frank M, Liefhold J, Wand F, et al. Assessment of analgesia in man: Tramadol controlled release formula vs tramadol standard formulation. Eur J Clin Pharmacol. 1996;51(1):31-8.

Pe´lissier T, Alloui A, Caussade F, Dubray C, Cloarec A, Lavarenne J, et al. Paracetamol exerts a spinal antinociceptive effect involving an indirect interaction with 5-hydroxytryptamine 3 receptors: in vivo and in vitro evidence. J Pharmacol Exp Ther. 1996;278(1):8-14.

Tao R, Ma Z, Auerbach SB. Alteration in regulation of serotonin release in rat dorsal raphe nucleus after prolonged exposure to morphine. J Pharmacol Exp Ther. 1998;286(1):481-8.

Kimura M, Obata H, Saito S. Antihypersensitivity effects of tramadol hydrochloride in a rat model of postoperative pain. Anesthesia and Analgesia. 2012;115(2):443-9.

Munro G, Baek CAE, Erichsen HK, Nielsen AN, Nielsen EØ, Scheel-Kruger J, et al. The novel compound (±)-1-[10-((E)-3-Phenyl-allyl)-3,10-diaza-bicyclo[4.3.1]dec-3-yl]-propan-1-one (NS7051) attenuates nociceptive transmission in animal models of experimental pain; a pharmacological comparison with the combined μ-opioid receptor agonist and monoamine reuptake inhibitor tramadol. Neuropharmacology. 2008;54(2):331-43.

Nelson EM, Philbrick AM. Avoiding Serotonin Syndrome: The nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Annals of Pharmacotherapeutics. 2012;46(12):1712-6.

Rojas-Corrales MO, Gibert-Rahola J, Micó JA. Tramadol induces antidepressant-type effects in mice. Life Sciences. 1998;63(12):175-80.

Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Micó JA. Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Life Sciences. 2002;72(2):143-52.

Driessen B, Reimann W, Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrenalin and dopamine in vitro. Br J Pharmacol. 1993;108(3):806-11.

Desmeules JA, Pigue, V, Collart L, Dayer P. Contribution of monoaminergic modulation to the analgesic effect of tramadol. Br J Clin Pharmacol. 1996;41(1):7-12.

Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clinical Pharmacokinetics. 2004;43(13):879-923.

Liu ZM, Zhou WH, Lian Z, Mu Y, Ren ZH, Cao JQ, et al. Drug dependence and abuse potential of tramadol. Acta Pharmacol Sin. 1999;20(1):52-4.

Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacological comparison of tramadol and morphine. Drug and Alcohol Dependence. 1991;27(1):7-17.

McQuay HJ. Pre-emptive analgesia: a systematic review of clinical studies. Annals of Medicine. 1995;27(2):249-56.

Faron-Górecka A, Kuœmider M, Inan SY, Siwanowicz J, Piwowarczyk T, Dziedzicka-Wasylewska M. Long-term exposure of rats to tramadol alters brain dopamine and α1-adrenoceptor function that may be related to antidepressant potency. Eur J Pharmacol. 2004;501(1-3):103-10.

Filip M, Wydra K, Inan SY, Dziedzicka-Wasylewska M, Przegaliński E. Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats. Eur J Pharmacol. 2004;498(1-3):143-51.

Yalcin I, Aksu F, Bodard S, Chalon S, Belzung C. Antidepressant-like effect of tramadol in the unpredictable chronic mild stress procedure: possible involvement of the noradrenergic system. Behavioral Pharmacology. 2007;18(7):623-31.

Gutstein HB, Akil H. Opioid Analgesics. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill Publishers; 2006:547.

Shipton EA. Tramadol: Present and future. Anaesthesia and Iintensive Care. 2000;28(4):363-74.

Goeringer KE, Logan BK, Christian GD. Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers. J Anal Toxicol. 1997;21(7):529-37.

Giusti P, Buriani A, Cima L, Lipartiti M. Effect of acute and chronic tramadol on [3H]-5HT uptake in rat cortical synaptosomes. Br J Pharmacol. 1997;122(2):302-6.

Cotman CW, Matthews DA. Synaptic plasma membranes from rat brain synaptosomes: Isolation and partial characterization. Biochim Biophys Acta. 1971;249(2):380-94.

Dodd PR, Hardy JA, Oakley AE, Edwardson JA, Perry EK, Delaunay JP. A rapid method for preparing synaptosomes: Comparison with alternative procedures. Brain Res. 1981;226(1):107-18.

Kodavanti PRS, Mundy WR, Tilson HA, Harry GJ. Effects of selected neuroactive chemicals on calcium transporting systems in rat cerebellum and on survival of cerebellar granule cells. Fundam Appl Toxicol. 1993;21(3):308-16.

Kari HP, Davidson PP, Herbert HH, Kochhar MH. Effects of ketamine on brain monoamines levels in rats. Research Communications in Chemical Pathology and Pharmacology. 1978;20(3):475-88.

Anden NE, Rool BE, Wegdininus B. On the occurrence of HVA in the brain and cerebrospinal fluid and its determination by fluorometric method. Life Sciences 1963;2(7):448-58.

Haubrich DR, Denzer JS. Simultaneous extraction and fluorometric measurement of brain serotonin, catecholamine, 5-HIIA and HVA. Anal Biochem. 1973;55(1):306-12.

Ansell GB, Beeson MF. A rapid and sensitive procedure for the combined assay of noradrenalin, dopamine and serotonin in single brain sample. Anal Biochem. 1968;23(2):196-206.

Dayer P, Collart L, Desmeules J. The pharmacology of tramadol. Drugs. 1994;47:3-7.

Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneim Forsch. 1996;46(11):1029-36.

Bloms-Funke P, Dremencov E, Cremers TIFH, Tzschentke TM. Tramadol increases extracellular levels of serotonin and noradrenalin as measured by in vivo microdialysis in the ventral hippocampus of freely-moving rats. Neurosci Lett. 2011;490(3):191-5.

Bosse KE, Maina FK, Birbeck JA, France MM, Roberts JJ, Colombo ML, et al. Aberrant striatal dopamine transmitter dynamics in brain-derived neurotrophic factor-deficient mice. J Neurochem. 2011;120(3):385-95.

Kharkevich DA, Churukanov VV. Pharmacological regulation of descending cortical control of the nociceptive processing. Eur J Pharmacol. 1999;375(1):121-31.

Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ. International union of pharmacology classification of receptors for 5- hydroxytryptamine (serotonin). Pharmacol Rev. 1994;46(2):157-203.

Benson GJ. Physiologic effects of pharmacological agents. Veterinary Clinical Services, Anesthesia and Analgesia. Yale Animal Resource Center, 2005.

Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA. 1988;85(14):5274-8.

Shyr MH, Tsai TH, Yang CH, Chen HM, Ng HF, Tan PPC. Propofol anesthesia increases dopamine and serotonin activities at the somato-sensory cortex in rats: A microdialysis study. Anesthesia and Analgesia. 1997;84(6):1344-8.

Honkanen A, Hyytiä P, Korpi EE, Ahtee L. Effects of morphine on metabolism of dopamine and serotonin in brains of alcohol-preferring AA and alcohol-avoiding ANA rats. Alcohol. 1999;18(1):3-10.

Yoshida Y, Koide S, Hirose N, Takada K, Tomiyama K, Koshikawa N, et al. Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors. Neuroscience. 1999;92(4):1357-65.

Sandrini M, Vitale M, Pini LA: Effect of rofecoxib on nociception and the serotonin system in the rat brain. Inflammation Res. 2002;51(3):154-9.

Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and non-opioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther. 1992;260(1):275-85.

Downloads

Published

2017-11-23

How to Cite

Panadanabiona, S. C. (2017). Alterations in aminergic system of rat brain by the opioid analgesic tramadol in the absence of pain-induction. International Journal of Basic & Clinical Pharmacology, 6(12), 2774–2782. https://doi.org/10.18203/2319-2003.ijbcp20175161

Issue

Section

Original Research Articles