Systemic and central effects of morphine on gastroduodenal motility

Gastrointestinal side effects still constitute a major drawback in both acute and chronic use of opioids. The exact mechanism behind the gastrointestinal effects is not known, but experimental studies indicate both central and peripheral actions. In an attempt to clarify to what extent the systemic effects of morphine after epidural administration contribute to the action on gastrointestinal motility, a study aiming to resemble the situation with epidural morphine was designed. Twenty healthy male volunteers were randomly allocated to two groups. Group one (n = 10) received intrathecal (0.4 mg) and intramuscular (4 mg) morphine (IT-IM-group). Group two (n = 10) received intrathecal (0.4 mg) morphine and i.m. saline (IT-group). Gastroduodenal activity was assessed by gastric emptying, manometry and electrogastrography. The plasma and urine concentrations of morphine and its inactive metabolite morphine-3-and active metabolite morphine-6-glucuronide were also determined. During the fasted state the gastrointestinal activity is characterised by a cyclic pattern with a duration of 80-120 min in the duodenum comprising three different phases with intense activity during Phase III. This pattern was seen in all volunteers. After the intrathecal administration the Phase III activity occurred significantly earlier in the IT-IM group (median 31 min; IR 34 min) compared to IT group (82 min; 37 min) (P < 0.01). The number of Phase IIIs was higher in the IT-IM group during the first 4 h after the morphine administration, compared to the IT group. However, after 6 h, there was no difference between the groups. The propagation velocity of Phase III decreased significantly in both groups (P < 0.001), but there was no difference between the groups. Tachygastria increased significantly with time in both groups. The acetaminophen absorption test showed that the area under the concentration curve (120 min) was significantly smaller in the IT-IM group compared to the IT group (P < 0.05). There were no measurable plasma concentrations of morphine or the glucoronidated metabolites M3G and M6G in the group that only received intrathecal morphine. This study showed that intrathecal morphine (0.4 mg) influenced gastroduodenal motility and that intramuscular morphine (4 mg) gave additional effects. These results might be applicable to the epidural situation and are indirect evidence that the gastroduodenal effects of epidural morphine are caused by both central and systemic effects of morphine.