Peripheral and preemptive opioid antinociception in a mouse visceral pain model

Recent studies suggest that opioids can produce analgesia through periphera l mechanisms following inflammation of peripheral tissue. This study examin ed whether opioids administered prior to inflammation can produce antinocic eption by peripheral mechanisms in a model of visceral pain. Mice were inje cted intraperitoneally (i.p.) with 1% acetic acid to evoke abdominal writhi ng, a standard model of visceral pain. The number of writhes: that occurred during 30 min after acetic acid were determined. Intraperitoneal injection of morphine sulfate (60, 90, 100 or 120 mug/0.3 ml) or the peripherally ac ting opioid loperamide (0.12, 0.36, 1.2 or 3.6 mg/0.3 ml) given 5 min after acetic acid decreased writhing in a dose-dependent fashion. Morphine (100 mug) produced an 70% attenuation in the number of writhes while loperamide (1.2 mg) decreased writhing by 56%. These antinociceptive effects were bloc ked by pretreatment with the opioid receptor antagonists naloxone (10 mg/kg ) and its quarternary version naloxone methiodide (10 mg/kg). To determine whether opioids produced preemptive antinociception via peripheral mechanis ms, mice received i.p. injections of morphine (1, 5, and 10 mug/0.3 ml) or vehicle 5 min before acetic acid. Doses of 5 and 10 mug morphine inhibited the number of writhes: by 51 and 93%, respectively. The highest dose ( 10 m ug) was ineffective when given intravenously 5 min before acetic acid, sugg esting that antinociception following i.p. administration was acting via pe ripheral mechanisms. These data demonstrate that low doses of opioids, give n before or after acetic acid, produce visceral antinociception through per ipheral mechanisms. This may be clinically relevant for the management of p ostoperative abdominal pain. (C) 2001 international Association for the Stu dy of Pain. Published by Elsevier Science B.V. All rights reserved.