Spinal and supraspinal effects of pertussis toxin on opioid analgesia.
The effects of in vivo pertussis toxin (PTX) treatment on the functional effects of opioid agonists were examined in the mouse. Mice were injected intracerebroventricularly (ICV), or intrathecally (IT), or IT and ICV with PTX, and dose-response studies of the antinociceptive action of systemic (SC) morphine, fentanyl, and etorphine were conducted 10 days later. IT PTX decreased the potency (approximately 4.5-fold) of morphine more than ICV administration (approximately 1.5-fold), whereas the combination of IT and ICV administration produced an additive effect. When PTX was administered spinally and supraspinally, the potency of morphine, fentanyl, and etorphine was reduced similarly (approximately 5-7-fold), indicating that the effect of PTX does does not vary considerably among agonists of different intrinsic efficacies. These studies indicate that in vivo PTX can reduce the potency of opioid agonists with different intrinsic efficacies, and that spinal mechanisms appear to be more sensitive to PTX treatment.
Shah
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Department of Pharmaceutical Sciences, College of Pharmacy, St. John's University, Queens, NY 11439.
Duttaroy
A
A
Davis
T
T
Yoburn
B C
BC
D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005283:Fentanyl / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D037342:Pertussis Toxin; D013116:Spinal Cord / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D009292:Narcotic Antagonists; D009294:Narcotics; D010566:Virulence Factors, Bordetella; D005048:Etorphine; D009020:Morphine; D037342:Pertussis Toxin; D005283:Fentanyl