What is it about?
Opioid-induced constipation is a major side-effect that limits the therapeutic utility of these excellent pain relievers. Unlike analgesic and euphoric effects, morphine- induced constipation persists with prolonged use as tolerance does not develop with chronic treatment. In this study we show that chronic morphine use results in colonic inflammation due to activation of enteric glia through connexin hemichannels.
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Why is it important?
In this study we show that colonic inflammtion due to prolonged exposure to morphine occurs as a result of the breakdown of the gut epithelial barrier resulting in bacterial translocation. Our findings further demonstrate that inhibition of connexin43 prevents colonic inflammation and reduces opioid-induced constipation thus providing a novel target for the treatment of chronic constipation due to opioid use.
Perspectives
Opioid-induced constipation persists with prolonged use. This study demonstrates that chronic morphine upregulates purinergic ion channels and connexin43 hemichannels in enteric glia, a major source for inflammatory mediators. These studies for the first time show that reducing colonic inflammation reverses opioid induced constipation and provides novel therapeutic targets.
Hamid Akbarali
Community Memorial Healthcenter
Read the Original
This page is a summary of: Connexin–purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation, The FASEB Journal, March 2017, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201601068r.
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