Evidence for an Action of Morphine and the Enkephalins on Sensory Nerve Endings in the Mouse Peritoneum

Abstract

1 A modification of the abdominal constriction test in mice has been developed, and used to study the antinociceptive effects of morphine and several related drugs. In most experiments, acetic acid (0.6% i.p.) was used as the nociceptive stimulus, and in a few cases, acetylcholine (3.2 mg/kg i.p.) was used. When the abdominal constriction response had reached a maximum, the drugs under test were given intraperitoneally, and their ability to decrease the number of abdominal constrictions was determined, beginning immediately after its administration. The aim of this study was to investigate the possibility that morphine and its congeners may produce an antinociceptive effect,by an action within the peritoneum.2 It was found that morphine was an extremely potent antinociceptive agent in this modified test, with an ID50 of 5.4 x 10-9 mol/kg (1.54 pg/kg). Codeine and pentazocine were about 40 times less active and oxymorphine was about twice as potent as morphine. Met-and Leu-enkephalin were also potent but their action diminished very rapidly with time. Ketocyclazocine was the most potent substance tested, and had an ID50 value of 1.26 x 10-10 mol/kg (0.036 ,ug/kg). All the drugs tested produced their maximal effect within 1 or 2 min of administration.3 Pretreatment of the mice with naloxone caused a dose-dependent shift to the right of the dose-response curve to morphine. The pAx plot was linear over part of the range, with a slope of -1.02 and the 'apparent pA2' value was 6.14. Naloxone was much less effective in antagonizing Met-enkephalin, and caused a slight potentiation of ketocyclazocine and pentazocine and of cocaine, which was used for comparison. 4 Pretreatment of mice with morphine, 3 h earlier, caused a marked tolerance to a subsequent dose of morphine, and a potentiation of the antagonist potency of naloxone. However, there was little cross-tolerance between morphine and Leu-enkephalin. 5 It is concluded that morphine and its congeners can produce an antinociceptive effect by an action within the mouse peritoneum, presumably by interacting with one or more types of opioid receptors which may be situated on sensory nerve endings.

Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice

“…Food and water were freely available. The abdominal constrictions resulting from intraperitoneal injection of acetic acid (0.6%), acetylcholine (4.5 mg kg-'), or kaolin suspension (50 mg kg-') consisting of a contraction of the abdominal muscle together with a stretching of hind limbs, were induced according to the procedures described previously (Collier et al, 1968;Bentley et al, 1981;Fujiyoshi et al, 1990 Animals were placed in separate boxes, and the number of abdominal constrictions was counted cumulatively over a period of 20 min for acetic acid and kaolin and 10 min for acetylcholine. The anti-hyperalgesic activity was expressed as the reduction of the number of abdominal constrictions between control animals (saline pretreated mice) and animals pretreated with NPC 18688 or with Hoe 140.…”

The efficacy of locally applied morphine in post‐operative pain after bilateral third molar surgery.

“…Local activity of the opioids when applied locally is reversed by naloxone [6,17,20,21,22] is dose-dependent and stereospecific. Most studies indicate that mu receptor ligands are the most important agonists, but delta and kappa-ligands are also active, depending upon the nature of the noxious stimuli [23].…”

Central Nervous System Depressant, Analgesic and Antidiarrheal Effects of the Seed Extracts of <i>Dimocarpus longan</i> Lour in Rats

“…The first method is extensively used for the assessment of peripheral antinociceptive activity [26]. It is very sensitive and able to detect anti-nociceptive effect of compounds at dose levels that may appear inactive in other methods such as the tailflick test [27]. The method has been associated with prostanoids in general, e.g., increased levels of PGE2 , PGF2α and lipoxygenase products in peritoneal fluids [28,29].…”