title: The effects of morphine and methylnaltrexone on gastrointestinal pain in healthy male participants.
abstract: BACKGROUND
  Opioid antagonists are increasingly used to abolish the gastrointestinal side effects of opioids. However, they can potentially interfere with local analgesia exerted via opioid receptors in the gut. Thus, in the current study we aimed to explore the effect of rectal morphine before and after blocking opioid receptors outside the central nervous system with methylnaltrexone (MNTX).
  
  
  METHODS
  In this randomized, placebo controlled, cross-over study 15 healthy male participants received the following drugs at three separate sessions: (i) placebo, (ii) 30 mg morphine administered per rectum, or (iii) 12 mg MNTX given subcutaneously before 30 mg rectal morphine. At baseline and after drug administration peripheral and central effects of the drugs were assessed by experimental pain to the skin, muscle, rectum and pupillometry.
  
  
  RESULTS
  Compared to placebo there was no local effect of morphine on mechanical rectal distension. In contrast, an increase in tolerated volume was seen following MNTX/morphine administration (p < 0.001), starting 7 min after dosing. Both morphine and MNTX/morphine had a central effect manifested as an increase in mechanical muscle pressure thresholds (both p < 0.001) and a decrease in pupil diameter (both p < 0.001). These effects occurred 30 min after dosing.
  
  
  CONCLUSIONS
  No peripheral analgesic effect of morphine was found. Methodological shortcomings may have contributed to the lack of peripheral analgesia and thus, a peripheral morphine effect on rectal pain cannot be excluded. On the other hand, the combination of MNTX and morphine exerted a local effect on rectal distensions and seems to improve analgesia.
authors: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
authors: A
authors: A
authors: Brokjaer
authors: A E
authors: AE
authors: Olesen
authors: L L
authors: LL
authors: Christrup
authors: A
authors: A
authors: Dahan
authors: A M
authors: AM
authors: Drewes
mesh_terms: D000285:Administration, Rectal; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012007:Rectum / Q000187:drug effects*; D012867:Skin / Q000187:drug effects; D059265:Visceral Pain; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D009020:Morphine
keywords: experimental pain; methylnaltrexone; morphine; peripheral analgesia; rectal administration