III - Prostaglandin hyperalgesia: relevance of the peripheral effect for the analgesic action of opioid-antagonists.
Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE2 or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.
D000700:Analgesics; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D006941:Hyperesthesia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009269:Nalorphine / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010423:Pentazocine / Q000008:administration & dosage / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D011458:Prostaglandins E; D009270:Naloxone; D009020:Morphine; D002351:Carrageenan; D010423:Pentazocine; D009269:Nalorphine