Analgesic effects of intrathecally-administered 3 alpha-hydroxy-5 alpha-pregnan-20-one in a rat mechanical visceral pain model.
Recent studies in animals have demonstrated that the steroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3A5P), is a potent analgesic when given intracerebroventricularly. Several studies in humans report that spinal steroids are effective in the treatment of chronic low-back pain when given in combination with morphine. The spinal antinociceptive effect of steroids, in particular a progesterone metabolite has not been studied in a visceral pain model. The experiments in the following study were designed to test, first, if the intrathecally-administered (i.t.) steroid, 3A5P, has analgesic properties in a mechanical visceral nociceptive assay, and second, if the intrathecal coadministration of this steroid and morphine is more effective than either therapy alone. Our mechanical visceral pain model (VPM) consists of a chronic indwelling duodenal balloon catheter implanted in the rat. The balloon is inflated to elicit a writhing response. Protection values are defined as the percentage of rats in each group which did not writhe. In this model, 3A5P was found to provide a dose-independent, though significant (p less than 0.01), antinociception when administered alone (33-67% protection vs. 0-25% for controls). Yet, protection offered by the coadministration of 3A5P and morphine (79%) was not significantly greater than that offered by morphine alone (85%). Unlike a dose and time-dependent response observed in a thermal cutaneous nociceptive assay, the antinociception of 3A5P was not dose-dependent when challenged with a mechanical visceral noxious stimulus.
Winfree
C J
CJ
Anesthesia Research Laboratory, Dartmouth-Hitchcock Medical Center, Lebanon, N.H. 03756.
Coombs
D W
DW
DeLeo
J A
JA
Colburn
R W
RW
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D000700:Analgesics; D009020:Morphine; D011280:Pregnanolone