Studies on the Development of Tolerance Following Spinal Analgetics

  • A. S. Tung
  • T. L. Yaksh
Part of the Anaesthesiologie und Intensivmedizin Anaesthesiology and Intensive Care Medicine book series (A+I, volume 158)


Many biologic responses secondary to opiate receptor interactions, both in vitro and in vivo, are subject to the development of tolerance. Thus, it would not be surprising to observe a decrease in the antinociceptive response to intrathecal or epidural opiates after prolonged use. Indeed, this phenomenon has been observed both clinically and in experimental animals.


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  1. 1.
    Tung AS, Wang JY, Yaksh TL (to be published) Tolerance to intrathecal opiates in the ratGoogle Scholar
  2. 2.
    Yaksh TL, Reddy SVR (to be published) Studies on the analgetic effects of intrathecal opiates, α-adrenergic agonists and baclofen: their pharmacology in the primate. AnesthesiologyGoogle Scholar
  3. 3.
    Tung AS, Yaksh TL (to be published) Evaluation of epidural opiates in the cat. 8th International congress of pharmacology, TokyoGoogle Scholar
  4. 4.
    Yaksh TL, Kohl RL, Rudy TA (1977) Induction of tolerance and withdrawal in rats receiving morphine in the spinal subarachnoid space. Eur J Pharmacol 42: 275–284PubMedCrossRefGoogle Scholar
  5. 5.
    Tung A, Maliniak K, Tenicela R, Winter PM (1980) Intrathecal morphine for intraoperative and postoperative analgesia. JAMA 244: 2637–2638PubMedCrossRefGoogle Scholar
  6. 6.
    Tung AS, Tenicela R, Winter PLM (1980) Opiate withdrawal syndrome following intrathecal administration of morphine. Anesthesiology 53: 340PubMedCrossRefGoogle Scholar
  7. 7.
    Ventafridda V, Figliuzzi M, Tamburini M, Gori E, Parolaro D, Sala M (1979) Clinical observation on analgesia elicited by intrathecal morphine in cancer patients. In: Bonica JJ et al (eds) Adv in pain research and therapy, vol 3. Raven, New York, pp 559–565Google Scholar
  8. 8.
    Lazorthes Y, Gouarderes Ch, Verdie JC, Monsarrat B, Bastide R, Campan L, Alwan A, Cros J (1980) Analgesie par injection intrathecale de morphine etude pharmacocinetique et application aux douleurs irreductibles. Neurochirurgie 26: 159–164PubMedGoogle Scholar
  9. 9.
    Onofrio B, Yaksh TL, Arnold PG (to be published) Continous low-dose intrathecal morphine administration in the treatment of chronic pain of malignant origin. Mayo Clin ProcGoogle Scholar
  10. 10.
    Müller H, Stoyanov M, Dorner U, Hempelmann G (to be published) opiates for relief of cancer pain. In: Yaksh TL, Müller H, Engquist A (eds) Anaesthesia and intensive care medicine. Springer, Berlin Heidelberg New YorkGoogle Scholar
  11. 11.
    Tung AS, Tenicela R, Barr G (to be published) Caudal opiates for pelvic cancer painGoogle Scholar
  12. 12.
    Zenz M, Piepenbrock S, Hilfrich J, Husch M (to be published) Pain therapy with epidural morphine in patients with terminal cancer. In: Yaksh TL, Müller H, Engquist A (eds) Anaesthesia and intensive care medicine. Springer, Berlin Heidelberg New YorkGoogle Scholar
  13. 13.
    Martin WR, Eades CG, Thompson J A, Huppler RD, Gilbert PE (1976) The effects of morphine and nalorphine-like drugs in the non-dependent and morphine dependent chronic spinal dog. J Pharmacol Exp Ther 197: 517–532PubMedGoogle Scholar
  14. 14.
    Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW (1977) Endogenous opioid peptides: multiple agonists and receptors, Nature 267: 495–499PubMedCrossRefGoogle Scholar
  15. 15.
    Fields NL, Emson PC, Leigh BK, Gilbert RFT, Iversen LL (1980) Multiple opiate receptors in primary afferent fibres. Nature 214: 351–352CrossRefGoogle Scholar
  16. 16.
    Tung AS, Yaksh TL (to be published) Involvement of multiple opiate receptors in spinally mediated analgesia. PainGoogle Scholar
  17. 17.
    Reddy SVR, Yaksh TL (1980) Antinociceptive effecs of lanthanum, neodymium and europium following intrathecal administration. Neuropharmacology 19: 181–185PubMedCrossRefGoogle Scholar
  18. 18.
    Yaksh TL, Wilson PR (1979) Spinal serotonin terminal system mediates antinociception. J Pharmacol Exp Ther 208: 446–453PubMedGoogle Scholar
  19. 19.
    Wilson PR, Yaksh TL (1978) Baclofen is antinociceptive in the spinal intrathecal space of animals. Eur J Pharmacol 51: 323–330PubMedCrossRefGoogle Scholar
  20. 20.
    Wang J-Y, Yasuoka S, Yaksh TL (to be published) Studies on the analgetic effect of intrathecal ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline): antagonism, tolerance and interaction with morphine. PharmacologistGoogle Scholar
  21. 21.
    Clineschmidt BV, McGuffin JC, Bunting PB (1979) Neurotensin: antinocisponsive action in rodents. Eur J Pharmacol 54: 129–138PubMedCrossRefGoogle Scholar
  22. 22.
    Colpaert FC, Niemegeers CJE, Janssen PAJ, Maroli AN (1980) The effects of prior fentanyl administration and of pain on fentanyl analgesia: tolerance to and enhancement of narcotic analgesia. J Pharmacol Exp Ther 213: 418–424PubMedGoogle Scholar
  23. 23.
    Siegel S, Hinson RE, Krank MD (1980) Morphine-induced attenuation of morphine tolerance. Science 212: 1533–1534CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • A. S. Tung
  • T. L. Yaksh

There are no affiliations available

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