Development of tolerance to antinociceptive effects of an intrathecal morphine/clonidine combination in rats

John L. Plummer, Patricia L. Cmielewski, Stephen Tallents, Pauline De La M. Hall, John Odontiadis, Geoffrey K. Gourlay, Harry Owen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Previous animal studies have shown the antinociceptive effects of intrathecal clonidine and intrathecal morphine to be synergistic. This study investigated the intrathecal administration of multiple doses of this drug combination to examine the rate of development of tolerance and to determine whether there was any toxic effect on the spinal cord. Rats with indwelling intrathecal catheters were given saline, morphine (2.5-7.5 μg), clonidine (17.5 μg), or clonidine (17.5 μg) plus morphine (1 μg) intrathecally twice daily for 41/2 days (total of 9 doses). Hot plate and tail flick tests were conducted after the first, fifth and ninth doses. After the ninth dose animals were killed and their spinal cords were removed for histological examination. Tolerance developed to the antinociceptive effects of the drug combination, but at a slower rate than to morphine alone. No evidence of toxicity or injury to the spinal cord was observed other than changes which could be ascribed to the presence of the catheter.

Original languageEnglish
Pages (from-to)618-623
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume351
Issue number6
DOIs
Publication statusPublished - Jun 1995
Externally publishedYes

Keywords

  • Alpha 2 adrenoceptor
  • Clonidine
  • Intrathecal
  • Morphine
  • Opioid tolerance
  • Spinal cord

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