It has been hypothesized that, in the absence of acute or chronic pain, a tonically active system exists involving opioid peptides, which ensures a certain level of pain insensitivity. Although various studies have failed to support this concept, it has been reported that in conditions of both experimentally induced and clinical pain, high doses of the opioid antagonist naloxone induced a state of hyperalgesia and thus seemed to set off this hypothetical system. Lower doses were, however, without effect or even acted as analgesics. This study investigated the effect of 5 and 20 mg naloxone i.v., compared to placebo, on the perception of pain in healthy humans. Pain was induced by two methods, using electrical and thermal stimulation of the skin, which have previously been shown to be sensitive to the effects of opioid as well as of non-steroidal anti-inflammatory analgesics. Each of 12 males and 12 females participated in 3 experimental sessions, in which the treatments were administered double-blind according to a Latin square design. Threshold and tolerance to electrically induced pain and threshold to thermally induced pain were measured at 30 min intervals for 90 min before and 90 min after drug administration. Electrical stimuli were square wave constant current impulses of linearly increasing intensity; thermal stimuli were of constant intensity and variable duration. Threshold and tolerance to electrically induced pain were not altered by either dose of naloxone, whereas the threshold to thermally induced pain was significantly higher after both 5 and 20 mg naloxone than after placebo, the effects of the two naloxone doses not differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies showed that symptoms of oesophageal motor disorders can be misinterpreted as indicating anorexia nervosa and that in primary anorexia nervosa gastric motility is frequently impaired. We investigated in 32 women with bulimia nervosa whether symptoms of oesophageal motor disorders could be obscured by or be mistaken as forming part of bulimic behaviour, and whether impaired gastric motility was frequent as well. Oesophageal motility was normal in 18 of26 patients studied, another four had incomplete lower eosophageal sphincter relaxation. Two patients had vigorous achalasia and each one achalasia and diffuse oesophageal spasm, all of whom experienced two types of vomiting: one selfinduced and one involuntary, in which the vomit was non-acidic and tasted as the preceding meal. Gastric emptying of a semisolid meal was studied in all patients except of the eight with oesophageal motor abnormalities. Emptying was significantly slower than in healthy controls and grossly delayed in nine of 24 patients.Antral contraction amplitudes were lower and increased less postcibally than in controls. In conclusion (i) bulimic behaviour can obscure symptoms of oesophageal motor disorders and (ii) gastric emptying is frequently delayed in bulimia nervosa.

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1. The selective 5‐HT3 receptor antagonist, ICS 205‐930 (Sandoz), has been reported to have potent effects on gastric smooth muscle in vivo and to enhance gastric emptying in animals and in man. 2. This study investigated the effects of ICS 205‐930 on fat‐delayed gastric emptying of a semisolid meal and antral motor activity in humans. 3. Twelve healthy men participated in each of three studies in which 10 or 20 mg of ICS 205‐930 or placebo were infused i.v. in a random double‐blind fashion. Gastric emptying and antral motor activity were studied scintigraphically. 4. Gastric emptying was not altered after 10 mg but slower after 20 mg of ICS 205‐930 than after placebo. Emptying after 20 mg of ICS 205‐930 was significantly slower than after 10 mg of ICS 205‐ 930. 5. Antral contraction amplitude was slightly lower after 20 mg of ICS 205‐930 than after placebo, whereas the effects of 10 mg ICS 205‐ 930 did not differ from those of placebo. 6. The results suggest that the investigated doses of ICS 205‐930 have only slight effects on gastric motor activity of healthy young men, with 20 mg reducing the rate of emptying.

In 53 consecutive patients with primary anorexia nervosa, gastric emptying of a semisolid meal was significantly slower than in 24 healthy subjects. Slow emptying tended to be associated with low serum potassium, low body weight, and long illness duration. Antral contraction amplitudes were lower than in healthy subjects and failed to increase postcibally, whereas contraction frequency and rhythmicity seemed unaffected. After the gastric prokinetic agent, cisapride, 8 mg intravenously administered double‐blind, emptying was significantly faster than after placebo. The recognition of impaired gastric motility may be important in the management of anorexia nervosa.

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1 Ro 15-8081 (Hoffmann-La Roche, Basle, Switzerland) is a novel mixed 5-HT/noradrenaline uptake inhibitor producing potent antinociceptive effects in animal pain models. 2 In healthy man, two models with electrically and thermally induced pain, respectively, have been shown to reliably discriminate between the effects of opioid as well as of antipyretic analgesics and placebo. 3 This study investigated the effects of single oral doses of 10, 25, and 50 mg Ro 15-8081 in comparison with 60 mg codeine and placebo on threshold and tolerance to electrically induced pain and on threshold to thermally induced pain. Furthermore, the effects on psychomotor function, self-rated subjective feelings, and side effect profile were studied. 4 Twenty healthy males participated each in five experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised two series of measurements before and twelve after drug administration, carried out at 30 min intervals. 5 Ro 15-8081 produced marked elevations of threshold and tolerance to electrically and of threshold to thermally induced pain. The effects of all doses of Ro 15-8081 were significantly superior to those of placebo. Threshold and tolerance to electrically induced pain were not affected differently by the three doses of Ro 15-8081, whereas the threshold to thermally induced pain was elevated significantly more by 50 mg than by 10 and 25 mg Ro 15-8081. 6 Codeine 60 mg had a more rapid onset of action and greater maximal effects than Ro 15-8081. 7 Psychomotor function, as measured by a reaction time and a fine motor control task, was not altered by any dose of Ro 15-8081, whereas 60 mg codeine produced a significant prolongation of reaction time. 8 Subjective feelings indicative of altered central nervous system arousal, well-being and mood were not influenced by Ro 15-8081. 9 Ro 15-8081 produced an only slightly higher number of side effects such as abdominal discomfort, headache, and nausea than did placebo.