Circular muscle contraction in the mice rectum plays a key role in morphine‐induced constipation. Issue 10 (13th July 2014)

• Record Type: Journal Article
• Authors: Ono, H.; Nakamura, A.; Matsumoto, K.; Horie, S.; Sakaguchi, G.; Kanemasa, T.
• Is Part Of: Neurogastroenterology & motility. Volume 26:Issue 10(2014:Oct.)
• Page Start: 1396
• Page End: 1407
• Publication Date: 2014-07-13
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12387
• Languages: English
• ISSNs: 1350-1925

Abstract

<abstract abstract-type="main" id="nmo12387-abs-0001"> <title>Abstract</title> <sec id="nmo12387-sec-0001" sec-type="section"> <title>Background</title> <p>Although opioids induce intestinal muscle contraction and provoke constipation, the intestinal region(s) that contribute to the constipation have remained unclear. We report here a region‐specific response of intestinal muscle contraction to morphine and its correlation with <italic>in vivo</italic> constipation.</p> </sec> <sec id="nmo12387-sec-0002" sec-type="section"> <title>Methods</title> <p>Regions of mice small and large intestines were dissected histologically and circular muscle contractile responses were measured using isometric transducers. Bead expulsion assays were performed to assess <italic>in vivo</italic> constipation.</p> </sec> <sec id="nmo12387-sec-0003" sec-type="section"> <title>Key Results</title> <p>The strongest contraction in response to morphine was detected in the rectum. The distal and transverse colon also showed strong contractions, whereas weak responses were detected in the proximal colon, jejunum, and ileum. Regarding the sustainability of muscle contractions during morphine exposure, prolonged waves were detected only in the rectum, while the waves diminished gradually in other regions. To identify the mechanism(s) underlying this difference, we focused on nitric oxide synthase (NOS). In the distal colon, decreased contraction during morphine exposure was recovered by application of a NOS inhibitor (L‐NAME), while a NOS substrate (L‐arginine) enhanced contractile degradation. In contrast L‐NAME and L‐arginine modestly affected the sustained contraction in the rectum. To confirm the correlation with constipation, beads were inserted into the transverse colon, distal colon, or rectum after morphine administration and expulsion times were examined. Beads tended to stop at the rectum even when inserted in the deeper colonic regions.</p> </sec> <sec id="nmo12387-sec-0004" sec-type="section"> <title>Conclusions & Inferences</title> <p>The rectum showed the greatest response to morphine in both <italic>in vitro</italic> and <italic>in vivo</italic> analyses, therefore it may play a key role for opioid‐induced constipation.</p> </sec> </abstract>