HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

High dose of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications.

Abstract
In rats with chronically implanted intrathecal catheters, high concentrations of morphine (3 microliters of 50 mg/ml: 150 micrograms) yielded a reliable and striking syndrome of pain behavior that involved intermittent bouts of biting and scratching at the dermatomes innervated by levels of the spinal cord proximal to the catheter tip. In addition, during intervals between bouts of agitation, the animals displayed a clear, marked hyperesthesia where an otherwise innocuous stimuli (brush stroke) evoked significant signs of discomfort and consequent aggressive behavior. These effects were exaggerated rather than reversed by high doses of naltrexone. The effect, perfectly mimicked by a considerably lower dose of morphine-3-glucuronide (15 micrograms) or the glycine antagonist strychnine (30 micrograms), was not produced by equimolar concentrations of sodium sulfate, glucuronide, methadone, or sufentanil. In halothane-anesthetized cats, light brushing of the hindpaw and tail or low-intensity stimulation of the sciatic nerves resulted in prominent elevations in blood pressure and pupil diameter following the intrathecal administration of high concentrations (50 mg/ml; 0.1 ml) of morphine sulfate. This effect, exaggerated by naloxone, was produced by a lower concentration of intrathecal morphine-3-glucuronide (5 mg/ml; 0.1 ml) but not by intrathecal saline. These results suggest the possibility that the effects of high doses of morphine may be characterized by a nonopiate receptor-mediated effect that alters the coding of sensory information in the spinal cord. The authors speculate that high concentrations of spinal opiates, as may be employed in tolerant terminal-cancer patients, could exert an action that physiologically antagonizes the analgesic effects otherwise mediated by the action of morphine on the spinal opiate receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsT L Yaksh, G J Harty, B M Onofrio
JournalAnesthesiology (Anesthesiology) Vol. 64 Issue 5 Pg. 590-7 (May 1986) ISSN: 0003-3022 [Print] UNITED STATES
PMID2938524 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Morphine Derivatives
  • Receptors, Drug
  • Sulfates
  • sodium sulfate
  • Naltrexone
  • Morphine
  • Sufentanil
  • Strychnine
  • morphine-3-glucuronide
  • Methadone
  • Fentanyl
Topics
  • Anesthesia, Spinal
  • Animals
  • Blood Pressure
  • Cats
  • Drug Tolerance
  • Fentanyl (analogs & derivatives, pharmacology)
  • Hyperesthesia (chemically induced, physiopathology)
  • Methadone (pharmacology)
  • Morphine (administration & dosage, pharmacology)
  • Morphine Derivatives (pharmacology)
  • Naltrexone (pharmacology)
  • Rats
  • Receptors, Drug (metabolism)
  • Stimulation, Chemical
  • Strychnine (pharmacology)
  • Sufentanil
  • Sulfates (pharmacology)
  • Touch

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: