Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. Pharmacological approaches taken to preserve the analgesic properties, while eliminating the unwanted side effects, have met with very limited success. Here, we provide evidence that altering mu opioid receptor regulation may provide a novel approach to discriminate morphine's beneficial and deleterious effects in vivo. We have previously reported that mice lacking the G protein-coupled receptor regulatory protein, beta-arrestin 2, display profoundly altered morphine responses. beta-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. In this report, we examine whether the side effects of morphine treatment are also augmented in this animal model. Surprisingly, the genetic disruption of opioid receptor regulation, while enhancing and prolonging analgesia, dramatically attenuates the respiratory suppression and acute constipation caused by morphine.
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PMID:Morphine side effects in beta-arrestin 2 knockout mice. 1591

Beta-arrestin 2 plays important physiological roles in regulating the function of the mu opioid receptor (muOR) in vivo. Periaqueductal gray (PAG) is a potential structure where morphine produces its antinociception, but it is unclear whether beta-arrestin 2 plays its regulatory effect on morphine at PAG. In the present study beta-arrestin 2 overexpression was induced by adenovirus at PAG of rats. Morphine was administrated in these rats through PAG microinjection and systemic administration. The antinociceptive effects of morphine were abolished in rats received microinjection of morphine at PAG and partially attenuated in rats received systemic administration of morphine. These findings support the notion that PAG is an important site where beta-arrestin 2 plays its regulatory effects on morphine analgesia.
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PMID:Decreased morphine analgesia in rat overexpressing beta-arrestin 2 at periaqueductal gray. 1656 22