TY - JOUR

T1 - The effects of morphine and methylnaltrexone on gastrointestinal pain in healthy male participants

AU - Brokjaer, A

AU - Olesen, A E

AU - Christrup, L L

AU - Dahan, A

AU - Drewes, A M

N1 - © 2015 John Wiley & Sons Ltd.

PY - 2015/5

Y1 - 2015/5

N2 - 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.KEY 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 & INFERENCES: 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.

AB - 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.KEY 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 & INFERENCES: 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.

KW - Administration, Rectal

KW - Adult

KW - Analgesics, Opioid

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Healthy Volunteers

KW - Humans

KW - Injections, Subcutaneous

KW - Male

KW - Middle Aged

KW - Morphine

KW - Muscle, Skeletal

KW - Naltrexone

KW - Narcotic Antagonists

KW - Pupil

KW - Quaternary Ammonium Compounds

KW - Rectum

KW - Skin

KW - Visceral Pain

KW - Young Adult

U2 - 10.1111/nmo.12545

DO - 10.1111/nmo.12545

M3 - Journal article

C2 - 25810023

VL - 27

SP - 693

EP - 704

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 5

ER -