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New insights into the role of endogenous opioids in the pathogenesis of gastrointestinal and liver disease
  1. Ali R Mani1,2,
  2. Kevin P Moore1
  1. 1
    Centre for Hepatology, Department of Medicine, UCL Medical School, University College London, London, UK
  2. 2
    Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  1. Dr Kevin Moore, Centre for Hepatology, Royal Free Campus, UCL Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK; kmoore{at}medsch.ucl.ac.uk

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Opiates have been known for centuries for their role in the management of pain. In 1975, Hughes and Kosterlitz isolated two endogenous peptides (enkephalins) from pig brain with high affinity for opioid receptors.1 Later, other groups of endogenous opioids, the endorphins, dynorphins and endomorphins were discovered. These endogenous opioid peptides bind to multiple opioid receptors (mu, delta and kappa) which belong to the G protein-coupled super-family of receptors. Initially the function of these peptides was thought to be limited to analgesia and the modulation of gastrointestinal motility; however, recent data have elucidated that endogenous opioids can regulate cell growth, differentiation and survival in non-neuronal systems such as inflammatory cells and biliary epithelia, as well as hepatic stellate cells.25

The involvement of endogenous opioids in the pathophysiology of gastrointestinal and hepatobiliary disease has been widely studied in recent years. The most significant observations directing the interest toward this field have been: (1) endogenous opioids exhibit anti-inflammatory properties in the gut and this effect may have implication in the management of inflammatory bowel disease;6 (2) biliary injury is associated with increased production of endogenous opioids7 and opioid receptor antagonists have a beneficial effect on pruritus of cholestasis;8 (3) endogenous opioids modulate hepatic stellate cell activation and opioid receptor antagonists show an anti-fibrotic effect in experimental models of hepatic fibrosis;4 5 (4) a novel opioid receptor (opioid growth factor receptor) has recently been identified which plays an important role in the negative regulation of cell proliferation in pancreatic cancer.9

The purpose of this brief review is to examine the available data concerning the role of endogenous opioids in the pathophysiology of gastrointestinal and liver disease and to discuss new therapeutic possibilities of opioid manipulation in gastrointestinal diseases.

Endogenous opioids and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, …

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