The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon

Paul T. Heitmann, Lauren Keightley, Lukasz Wiklendt, David A. Wattchow, Simon S.J. Brookes, Nicholas J. Spencer, Marcello Costa, Phil G. Dinning

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In most animal species, opioids alter colonic motility via the inhibition of excitatory enteric motor neurons. The mechanisms by which opioids alter human colonic motility are unclear. The aim of this study was to describe the effects of loperamide on neuromuscular function in the human colon. Methods: Tissue specimens of human colon from 10 patients undergoing an anterior resection were divided into three inter-taenial circular muscle strips. Separate organ baths were used to assess: (1) excitatory transmission (selective blockade of inhibitory transmission: L-NOARG/MRS2179); (2) inhibitory transmission (selective blockade of excitatory transmission: hyoscine hydrobromide); and (3) a control bath (no drug additions). Neuromuscular function was assessed using force transducer recordings and electrical field stimulation (EFS; 20 V, 10 Hz, 0.5 ms, 10 s) prior to and following loperamide and naloxone. Key Results: In human preparations with L-NOARG/MRS2179, loperamide had no significant effects on isometric contractions. In preparations with hyoscine hydrobromide, loperamide reduced isometric relaxation during EFS (median difference + 0.60 g post-loperamide, Z = −2.35, p = 0.019). Conclusions and Inferences: Loperamide had no effect on excitatory neuromuscular function in human colonic circular muscle. These findings suggest that loperamide alters colonic function by acting primarily on inhibitory motor neurons, premotor enteric neurons, or via alternative non-opioid receptor pathways.

Original languageEnglish
Article numbere14442
Number of pages10
JournalNeurogastroenterology and Motility
Early online date21 Aug 2022
DOIs
Publication statusE-pub ahead of print - 21 Aug 2022

Keywords

  • analgesics
  • colon
  • constipation
  • enteric nervous system
  • gastrointestinal motility
  • loperamide
  • opioid

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