Cholestasis in the male rat is associated with naloxone-reversible antinociception.

J Hepatol

Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Published: January 1994

AI Article Synopsis

  • Evidence suggests that cholestasis leads to increased activity in the opioid system of the central nervous system, potentially reducing pain response.
  • In a rat study, those with cholestasis showed significantly longer tail-flick latencies, indicating a higher pain threshold compared to controls.
  • Naloxone selectively reversed the pain relief effect in cholestasis, confirming that this increased pain tolerance is opioid-receptor mediated, unlike in other liver damage models.

Article Abstract

Clinical observations have suggested that cholestasis is associated with increased neurotransmission mediated by the opioid system in the central nervous system. As opiate agonists (e.g. morphine) mediate analgesia, increased opioidergic tone in cholestasis should be associated with a decreased response to pain. To test this hypothesis, the response of rats with acute cholestasis to a nociceptive stimulus was measured by the use of the tail-flick test, an extensively validated assay for measuring opiate-induced antinociception. Five and 7 days after bile-duct resection, the mean tail-flick latency was longer than before surgery (p < 0.05), whereas the corresponding means for unoperated and sham-resected controls were not significantly different from their respective baseline values. The increase in the mean tail-flick latency in the bile-duct resection group was reversed by (-)-naloxone (1 mg/kg subcutaneously), but not by its enantiomer (+)-naloxone (10 mg/kg subcutaneously) (p < 0.001). The stereoselective reversal of antinociception in cholestasis by naloxone indicates that this phenomenon is opioid-receptor mediated. In contrast, prolongation of the mean TFL found in the rat model of thioacetamide-induced acute hepatocellular necrosis was not reversed by (-)-naloxone, indicating that antinociception in this model is not opioid mediated. These findings provide support for the hypothesis that cholestasis is associated with increased opioidergic tone.

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http://dx.doi.org/10.1016/s0168-8278(05)80471-4DOI Listing

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