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.

  • Review
  • Published:

Nalbuphine, a non-controlled opioid analgesic, and its potential use in research mice

Lab Animal volume 44, pages 106–110 (2015)Cite this article

Abstract

Nalbuphine is an inexpensive, non-controlled, opioid analgesic that has been in clinical use for decades. A kappa opioid receptor agonist and mu opioid receptor antagonist, nalbuphine causes fewer adverse effects than other opioid analgesics. The author reviews the characteristics of nalbuphine, analyzes studies of nalbuphine in mice and explores the potential use of nalbuphine to treat pain in research mice. In analgesiometric studies in mice, nalbuphine ameliorates both somatic and visceral pain. Nalbuphine seems to have a broad range of safe doses for subcutaneous administration in mice. Unlike non-steroidal anti-inflammatory drugs, nalbuphine does not antagonize prostaglandins or impede labor in mice. Although additional study is needed before clinical use can be recommended, evidence presented here suggests that nalbuphine might be an effective analgesic for dystocia (or difficult birth) and other painful conditions in research mice.

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. National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals Recognition and Alleviation of Pain in Laboratory Animals (National Academies Press, Washington, DC, 2009).

  2. ACLAM Guidelines for the Assessment and Management of Pain in Rodents and Rabbits (July 2006) http://www.aclam.org/education-and-training/position-statements-and-reports.

  3. Narver, H.L. Oxytocin in the treatment of dystocia in mice. J. Am. Assoc. Lab. Anim. Sci. 51, 10–17 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Fish, R.E., Brown, M.J., Danneman, P.J. & Karas, A.Z. (eds.) Anesthesia and Analgesia in Laboratory Animals 2nd edn. (Elsevier, London, 2008).

    Google Scholar 

  5. Fox, J.G. et al. (eds.) The Mouse in Biomedical Research: Diseases vol. 2, 2nd edn. (Academic, Burlington, MA, 2007).

    Google Scholar 

  6. Winchester, S.K. et al. Coordinate regulation of prostaglandin metabolism for induction of parturition in mice. Endocrinology 143, 2593–2598 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Errick, J.K. & Heel, R.C. Nalbuphine. A preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 26, 191–211 (1983).

    Article  CAS  PubMed  Google Scholar 

  8. Kshirsagar, S., Gear, R., Levine, J. & Verotta, D. A mechanistic model for the sex-specific response to nalbuphine and naloxone in postoperative pain. J. Pharmacokinet. Pharmacodyn. 35, 69–83 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Woollard, M. et al. Less IS less: a randomized controlled trial comparing cautious and rapid nalbuphine dosing regimens. Emerg. Med. J. 21, 362–364 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gunion, M.W., Marchionne, A.M. & Anderson, C.T.M. Use of the mixed agonist-antagonist nalbuphine in opioid based analgesia. Acute Pain 6, 29–39 (2004).

    Article  CAS  Google Scholar 

  11. Anderson, D. A review of systemic opioids commonly used for labor pain relief. J. Midwifery Womens Health 56, 222–239 (2011).

    Article  PubMed  Google Scholar 

  12. Benson, G.J. & Tranquilli, W.J. Advantages and guidelines for using opioid agonist-antagonist analgesics. Vet. Clin. North Am. Small Anim. Pract. 22, 363–365 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Pick, C.G., Paul, D. & Pasternak, G.W. Nalbuphine, a mixed kappa1 and kappa3 analgesic in mice. J. Pharmacol. Exp. Ther. 262, 1044–1050 (1992).

    CAS  PubMed  Google Scholar 

  14. Patrick, C.A., Holden Ko, M.C. & Woods, J.H. Comparison of antinociceptive effects induced by kappa opioid agonists in male and female mice. Analgesia (Elmsford NY) 4, 397–404 (1999).

    Article  CAS  Google Scholar 

  15. Wong, C.L. & Wai, M.K. Increased naloxone potency induced by pretreatment with morphine and nalbuphine in mice. Clin. Exp. Pharmacol. Physiol. 11, 301–307 (1984).

    Article  CAS  PubMed  Google Scholar 

  16. Wong, C.-L. The effect of nalbuphine on gastrointestinal transit in mice. Eur. J. Pharmacol. 135, 219–223 (1987).

    Article  CAS  PubMed  Google Scholar 

  17. Stav, A., Rabinowitz, R. & Korczyn, A.D. Actions of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice. J. Anesth. 6, 439–445 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Ortiz, M.I. et al. Evaluation of the interaction between acemetacin and opioids on the Hargreaves model of thermal hyperalgesia. Pharmacol. Biochem. Behav. 88, 47–54 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Drug Enforcement Administration, Office of Diversion Control, Drug and Chemical Evaluation Section. Nalbuphine Hydrochloride (August 2013). http://www.deadiversion.usdoj.gov/drug_chem_info/nalbuphine.pdf.

  20. Hospira, Inc. Material Safety Data Sheet: Nalbuphine Hydrochloride Injection. http://www.hospira.com/Images/MSDS_Nalbuphine_Hydrochloride_Injection_060214_81-95520_1.pdf.

  21. Definition of Controlled Substance Schedules http://www.deadiversion.usdoj.gov/schedules/.

  22. Liao, C.C. et al. Efficacy of intramuscular nalbuphine versus diphenhydramine for the prevention of epidural morphine-induced pruritus after cesarean delivery. Chang Gung Med. J. 34, 172–178 (2011).

    PubMed  Google Scholar 

  23. Kim, T.H., Kim, J.M., Lee, H.H., Chung, S.H. & Hong, Y.P. Effect of nalbuphine hydrochloride on the active phase during first stage of labor: a pilot study. J. Obstet. Gynaecol. 31, 724–727 (2011).

    Article  CAS  PubMed  Google Scholar 

  24. Wagner, A.E., Worland, G.A., Glawe, J.C. & Hellyer, P.W. Multicenter, randomized controlled trial of pain-related behaviors following routine neutering in dogs. J. Am. Vet. Med. Assoc. 233, 109–115 (2008).

    Article  PubMed  Google Scholar 

  25. Lee, C.H., Lin, S.L., Chi, T.T., Chang, S.H. & Wang, H.C. Effect of topical administration of 0.8% nalbuphine on the cornea of dogs after phacoemulsification. J. Vet. Med. Sci. 75, 1041–1047 (2013).

    Article  CAS  PubMed  Google Scholar 

  26. Coetzee, J.F., Lechtenberg, K.F., Stock, M.L. & Kukanich, B. Pharmacokinetics and effect of intravenous nalbuphine in weaned Holstein calves after surgical castration. J. Vet. Pharmacol. Ther. 37, 169–177 (2014).

    Article  CAS  PubMed  Google Scholar 

  27. Ho, S.T. et al. The antinociceptive effect of long-acting nalbuphine preparation in rabbits. Acta Anaesthesiol. Sin. 41, 99–103 (2003).

    PubMed  Google Scholar 

  28. Kruger, L. (ed.) Methods in Pain Research (CRC, Boca Raton, FL, 2001).

    Book  Google Scholar 

  29. Kuzmin, A.V., Gerrits, M.A.F.M., Zvartau, E.E. & van Ree, J.M. Influence of buprenorphine, butorphanol, and nalbuphine on the initiation of intravenous cocaine self-administration of drug naïve mice. Eur. Neuropsychopharmacol. 10, 447–454 (2000).

    Article  CAS  PubMed  Google Scholar 

  30. Frey, H.H. Effect of mu- and kappa- opioid agonists on the electroconvulsive seizure threshold of mice and antagonism by naloxone and MR 2266. Pharmacol. Toxicol. 62, 150–154 (1988).

    Article  CAS  PubMed  Google Scholar 

  31. Skoulis, N.P., James, R.C., Harbison, R.D. & Roberts, S.M. Depression of hepatic glutathione by opioid analgesic drugs in mice. Toxicol. Appl. Pharmacol. 99, 139–147 (1989).

    Article  CAS  PubMed  Google Scholar 

  32. Gringauz, M., Rabinowitz, R., Stav, A. & Korczyn, A.D. Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine. J. Anesth. 15, 204–209 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Horn, C.C. The medical implications of gastrointestinal vagal afferent pathways in nausea and vomiting. Curr. Pharm. Des. 20, 2703–2712 (2014).

    Article  CAS  PubMed  Google Scholar 

  34. Liu, Y.-L., Malik, N., Sanger, G.J., Friedman, M.I. & Andrews, P.L.R. Pica-A model of nausea? Species differences in response to cisplatin. Physiol. Behav. 85, 271–277 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Ratajczak, C.K. & Muglia, L.J. Insights into parturition biology from genetically altered mice. Pediatr. Res. 64, 581–589 (2008).

    Article  PubMed  Google Scholar 

  36. US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, and United States Department of Agriculture Policy #11.

  37. Rätsep, M.T., Barette, 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. Gades, N.M., Danneman, P.J., Wixson, S.K. & Tolley, E.A. The magnitude and duration of morphine, butorphanol, and buprenorphine in rats and mice. Contemp. Top. Lab. Anim. Sci. 39, 8–13 (2000).

    CAS  PubMed  Google Scholar 

  39. Chu, K.-S., Wang, J.-J., Hu, O.Y.-P., Ho, S.-T. & Chen, Y.-W. The antinociceptive effect of nalbuphine and its long-acting esters in rats. Anesth. Analg. 97, 806–809 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Liu, K.S. et al. Antinociceptive effect of a novel long-acting nalbuphine preparation. Br. J. Anaesth. 92, 712–715 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Animal Health and Care Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

    Heather Lyons Narver

Authors
  1. Heather Lyons Narver
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heather Lyons Narver.

Ethics declarations

Competing interests

The author declares 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

Narver, H. Nalbuphine, a non-controlled opioid analgesic, and its potential use in research mice. Lab Anim 44, 106–110 (2015). https://doi.org/10.1038/laban.701

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban.701

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