Differential cross-tolerance between intrathecal morphine and sufentanil in the rat

Anesthesiology. 1990 Dec;73(6):1141-7. doi: 10.1097/00000542-199012000-00012.


By means of a subcutaneously implanted osmotic pump, groups of rats received a constant-rate (1 microliter/h), 7-day intrathecal infusion of saline or one of two mu opioid agonists: sufentanil (0.6 nmol/h) or morphine (20 nmol/h). These concentrations of morphine and sufentanil yielded a comparable near maximal hot-plate response latency on day 1 of the infusion. On day 7, the magnitude of tolerance was assessed in each group by establishing intrathecal dose-response curves and ED50 values for sufentanil and morphine given as a bolus injection. Each infused animal was used for a single bolus injection. In all cases, infusion with the opioid resulted in a rightward shift (increase in ED50) for both morphine and sufentanil as compared to saline-infused animals. The magnitude of the shift, however, was different for the two drugs. Thus in morphine-infused rats, the morphine ED50 increased as compared to saline-infused animals by a factor of 44, whereas the sufentanil ED50 shifted by a factor of 10. In sufentanil-infused animals, the respective shifts in the morphine and sufentanil ED50 values were increased by a factor of 9 and 3, respectively. Thus, a significantly greater shift as compared to saline-infused animals was observed in morphine-infused than in sufentanil-infused animals. Conversely, regardless of the opioid to which the animal was exposed, morphine-tested animals showed a greater rightward shift than did sufentanil-tested animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology
  • Animals
  • Drug Tolerance / physiology
  • Fentanyl / administration & dosage
  • Fentanyl / analogs & derivatives*
  • Fentanyl / pharmacology
  • Infusion Pumps, Implantable
  • Injections, Spinal
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Sufentanil


  • Analgesics, Opioid
  • Receptors, Opioid
  • Morphine
  • Sufentanil
  • Fentanyl