Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Note
  • Published:

Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery

Lab Animal volume 43, pages 167–172 (2014)Cite this article

Abstract

Embryo transfer is a surgical technique that is widely used in reproductive biotechnology. Despite the ethical obligation to relieve animals' post-operative pain, analgesia is not routinely provided after embryo transfer surgery because it has been suggested that analgesics may be detrimental to embryo survival. Studies suggest, however, that the potential for adverse effects varies depending on the type of analgesic used and the timing of its administration. The authors carried out a study to determine whether pre-operatively administered tramadol, a synthetic analogue of codeine, influenced birth rate, litter survival or the post-operative body weights of surrogate dams. Compared with controls that were not given any analgesic, surrogate dams given tramadol had similar birth rates and similar body weights at all time points. The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning. The authors conclude that pre-operatively administered tramadol does not harm the success rate of embryo transfer surgery and even may improve litter survival.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Goulding, D.R. et al. The effects of perioperative analgesia on litter size in Crl:CD1(ICR) mice undergoing embryo transfer. J. Am. Assoc. Lab. Anim. Sci. 49, 423–426 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Parker, J.M., Austin, J., Wilkerson, J. & Carbone, L. Effects of multimodal analgesia on the success of mouse embryo transfer surgery. J. Am. Assoc. Lab. Anim. Sci. 50, 466–470 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. American College of Laboratory Animal Medicine. Guidelines for the Assessment and Management of Pain in Rodents and Rabbits (Public Statement, ACLAM, 2007). (http://www.aclam.org/Content/files/files/Public/Active/position_pain-rodent-rabbit.pdf).

  4. Lee-Parritz, D. Analgesia for rodent experimental surgery. Isr. J. Vet. Med. 62, 3–4 (2007).

    Google Scholar 

  5. Interagency Research Animal Committee. U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (Office of Science and Technology Policy, Washington, DC, 1985).

  6. Yentis, S., May, A. & Malhotra, S. Analgesia, Anaesthesia and Pregnancy: A Practical Guide 2nd edn. (Cambridge University Press, Cambridge, UK, 2007).

    Book  Google Scholar 

  7. Kona-Boun, J.J., Silim, A. & Troncy, E. Immunologic aspects of veterinary anesthesia and analgesia. J. Am. Vet. Med. Assoc. 226, 355–363 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. McGuire, L. et al. Pain and wound healing in surgical patients. Ann. Behav. Med. 31, 165–172 (2006).

    Article  PubMed  Google Scholar 

  9. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 8th edn. (National Academies Press, Washington, DC, 2011).

  10. Joshi, G.P. & Ogunnaike, B.O. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol. Clin. North America 23, 21–36 (2005).

    Article  PubMed  Google Scholar 

  11. Thaete, L.G., Levin, S.I. & Dudley, A.T. Impact of anesthetics and analgesics on fetal growth in the mouse. Lab. Anim. 47, 175–183 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chiang, C.N. & Lee, C.C. (eds.) Prenatal Drug Exposure: Kinetics and Dynamics, NIDA Research Monograph Series #60 (U.S. Department of Health and Human Services, Rockville, MD, 1985).

    Google Scholar 

  13. Simmons, R.D., Miller, R.K. & Kellogg, C.K. Prenatal diazepam: distribution and metabolism in perinatal rats. Teratology 28, 181–188 (1983).

    Article  CAS  PubMed  Google Scholar 

  14. Littleford, J. Effects on the fetus and newborn of maternal analgesia and anesthesia: a review. Can. J. Anaesth. 51, 586–609 (2004).

    Article  PubMed  Google Scholar 

  15. Parboosingh, J. The effects of medication during pregnancy. Can. Fam. Physician 27, 1013–1015 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Dorsch, M.M., Otto, K. & Hedrich, H.J. Does preoperative administration of metamizol (Novalgin) affect postoperative body weight and duration of recovery from ketamine-xylazine anaesthesia in mice undergoing embryo transfer: a preliminary report. Lab. Anim. 38, 44–49 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Valle, M., Garrido, M.J., Pavón, J.M., Calvo, R. & Trocóniz, I.F. Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (−)-O-desmethyltramadol, in rats. J. Pharmacol. Exp. Ther. 293, 646–653 (2000).

    CAS  PubMed  Google Scholar 

  18. Hummel, T. et al. Assessment of analgesia in man: tramadol controlled release formula vs. tramadol standard formulation. Eur. J. Clin. Pharmacol. 51, 31–38 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Miranda, H.F. & Pinardi, G. Antinociception, tolerance, and physical dependence comparison between morphine and tramadol. Pharmacol. Biochem. Behav. 61, 357–360 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Gebhardt, G.F. & Schmidt, R.F. (eds.) Encyclopedia of Pain 2nd edn. (Springer, New York, 2007).

    Google Scholar 

  21. Hennies, H.H., Friderichs, E. & Schneider, J. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittelforschung 38, 877–880 (1988).

    CAS  PubMed  Google Scholar 

  22. Raffa, R.B. & Fridericks, E. The basic science aspect of tramadol hydrochloride. Pain Rev. 3, 249–271 (1996).

    CAS  Google Scholar 

  23. Raffa, R.B. et al. Opioid and non-opioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. J. Pharmacol. Exp. Ther. 260, 275–285 (1992).

    CAS  PubMed  Google Scholar 

  24. Bamigbade, T.A., Davidson, C., Langford, R.M. & Stamford, J.A. Actions of tramadol, its enantiomers and principle metabolite, O-desmethyltramadol on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. Br. J. Anaesth. 79, 352–356 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Grond, S. & Sablotzki, A. Clinical pharmacology of tramadol. Clin. Pharmacokinet. 43, 879–923 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Symeon, E. et al. Evaluation of the analgesic effect of tramadol in two different strains of mice. Proceedings of the 35th Scientific Conference of the Hellenic Society for Biological Science (Nafplio, Greece, 23–25 May 2013).

  27. Coetzee, J.F. & van Loggerenberg, H. Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. Br. J. Anaesth. 81, 737–741 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Houmes, R.J. et al. Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Anesth. Analg. 74, 510–514 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Matthiesen, T., Wöhrmann, T., Coogan, T.P. & Uragg, H. The experimental toxicology of tramadol: an overview. Toxicol. Lett. 95, 63–71 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Hariharan, S., Moseley, H., Kumar, A. & Raju, S. The effect of preemptive analgesia in postoperative pain relief—a prospective double-blind randomized study. Pain Med. 10, 49–53 (2009).

    Article  PubMed  Google Scholar 

  31. Kissin, I. Preemptive analgesia at the crossroad. Anesth. Analg. 100, 754–756 (2005).

    Article  PubMed  Google Scholar 

  32. Baumans, V. Science-based assessment of animal welfare: laboratory animals. Rev. Sci. Tech. 24, 503–513 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Broom, D.M. Animal welfare: concepts and measurement. J. Anim. Sci. 69, 4167–4175 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union 276, 33–79 (2010).

  35. Nicklas, W. et al. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36, 20–42 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. American Veterinary Medical Association. Guidelines for the Euthanasia of Animals: 2013 Edition (AVMA, Schaumberg, IL, 2013). (https://www.avma.org/kb/policies/documents/euthanasia.pdf).

  37. Rätsep, M.T., Barrette, V.F., Winterborn, A., Adams, M.A. & Croy, B.A. Hemodynamic and behavioral differences after administration of meloxicam, buprenorphine, or tramadol as analgesics for telemeter implantation in mice. J. Am. Assoc. Lab. Anim. Sci. 52, 560–566 (2013).

    PubMed  PubMed Central  Google Scholar 

  38. Liles, J.H., Flecknell, P.A., Roughan, J. & Cruz-Madorran, I. Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat. Lab. Anim. 32, 149–161 (1998).

    Article  CAS  PubMed  Google Scholar 

  39. Wiesenfeld-Hallin, Z. Sex differences in pain perception. Gend. Med. 2, 137–145 (2005).

    Article  PubMed  Google Scholar 

  40. McLaren, A. & Michie, D. Studies on the transfer of fertilized mouse eggs to uterine foster-mothers. I. Factors affecting the implantation and survival of native and transferred eggs. J. Exp. Biol. 33, 394–416 (1956).

    Google Scholar 

  41. Nagy, A., Gertsenstein, M., Vintersten, K. & Behringer, R. Manipulating the Mouse Embryo: A Laboratory Manual 3rd edn. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2003).

    Google Scholar 

  42. Auerbach, A.B. et al. Strain-dependent differences in the efficiency of transgenic mouse production. Transgenic Res. 12, 59–69 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Bagis, H., Odaman Mercan, H. & Dinnyes, A. Exposure to warmer postoperative temperatures reduces hypothermia caused by anaesthesia and significantly increases the implantation rate of transferred embryos in the mouse. Lab. Anim. 38, 50–54 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Luo, C. et al. Superovulation strategies for 6 commonly used mouse strains. J. Am. Assoc. Lab. Anim. Sci. 50, 471–478 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Kamjoo, M., Brison, D.R. & Kimber, S.J. Apoptosis in the preimplantation mouse embryo: effect of strain difference and in vitro culture. Mol. Reprod. Dev. 61, 67–77 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory Animal Facilities, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    Elda Koutroli,  Paul Alexakos,  Zacharias Kakazanis,  Irene Symeon,  Evangelos Balafas &  Nikolaos Kostomitsopoulos

  2. Department of Medical Laboratories, Faculty of Health and Caring Professions, Technological Educational Institute of Athens, Athens, Greece

    Elda Koutroli,  Irene Symeon &  Chrysa Voyiatzaki

Authors
  1. Elda Koutroli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Alexakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zacharias Kakazanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irene Symeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Evangelos Balafas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chrysa Voyiatzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nikolaos Kostomitsopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikolaos Kostomitsopoulos.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koutroli, E., Alexakos, P., Kakazanis, Z. et al. Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery. Lab Anim 43, 167–172 (2014). https://doi.org/10.1038/laban.518

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban.518

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing