Peripherally Acting Mediators of Pain and Analgesia Potentiate the Central Analgesic Effects of Fentanyl and Analgin (Dipyrone) in Rats.

Intramuscular administration of the central analgesics fentanyl and Analgin (dipyrone) along with the pain mediators cholecystokinin (CCK), glutamate, ATP, and adrenaline, and the analgesia mediator adenosine, which have weak penetration into the CNS, induced maximal analgesic effects at minimally effective doses in the tailflick test in rats. The minimal effective doses of Analgin and fentanyl decreased by factors of 50–220 in response to combined i.m. administration of each of the analgesics with CCK, glutamate, ATP, adrenaline, and adenosine at subthreshold does which were ineffective when given alone. Intragastric administration of lidocaine and subdiaphragmatic gastric vagotomy completely blocked the analgesic effects of these combinations. These data lead to the conclusion that peripherally acting pain and analgesia mediators given systemically potentiate the central analgesic actions of Analgin and fentanyl via stimulation of the chemoreceptors of vagal afferents in the gastric mucosa. [ABSTRACT FROM AUTHOR]