Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability
by
Crain SM, Shen KF.
Department of Neuroscience,
Albert Einstein College of Medicine,
Yeshiva University, Bronx, New York, USA.
smcrain@aecom.yu.edu
Pain 2000 Feb;84(2-3):121-31

ABSTRACT

Recent preclinical and clinical studies have demonstrated that cotreatments with extremely low doses of opioid receptor antagonists can markedly enhance the efficacy and specificity of morphine and related opioid analgesics. Our correlative studies of the cotreatment of nociceptive types of dorsal-root ganglion neurons in vitro and mice in vivo with morphine plus specific opioid receptor antagonists have shown that antagonism of Gs-coupled excitatory opioid receptor functions by cotreatment with ultra-low doses of clinically available opioid antagonists, e.g. naloxone and naltrexone, markedly enhances morphine's antinociceptive potency and simultaneously attenuates opioid tolerance and dependence. These preclinical studies in vitro and in vivo provide cellular mechanisms that can readily account for the unexpected enhancement of morphine's analgesic potency in recent clinical studies of post-surgical pain patients cotreated with morphine plus low doses of naloxone or nalmefene. The striking consistency of these multidisciplinary studies on nociceptive neurons in culture, behavioral assays on mice and clinical trials on post-surgical pain patients indicates that clinical treatment of pain can, indeed, be significantly improved by administering morphine or other conventional opioid analgesics together with appropriately low doses of an excitatory opioid receptor antagonist.

DAMGO
Arrestin
G protein
Morphine
Tramadol
Oxycodone
Mechanisms
Peroxynitrite
Endomorphins
Novelty and pain
Receptor regulation
Glycine anatagonists
Fentanyl and ketamine
Signalling mechanisms
The extended amygdala
Opioids, mood and cognition
Tolerance, sensitization and dependence
Anxiety, opioids, cholecystokinin and tolerance

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