Circadian rhythm of pain in male mice.

1. Circadian rhythm of pain in response to the thermal stimuli was assessed in male mice. 2.

Stressors and pain sensitivity in CFW mice. Role of opioid peptides.

Effects of several environmental situations on pain threshold were studied in CFW male mice. Immobilization induced significant and naloxone reversible analgesia. Isolation produced analgesia which was partially reversed by naloxone.

Bivalent opioid peptide analogues with reduced distances between pharmacophores.

To investigate the role of distance between two opioid peptide pharmacophores on in vitro and in vivo activities, three new bivalent opioid analogues have been synthesized in which the dipeptide Tyr-D-Phe was connected with diamine moieties ("bridges"). The analogue with a hydrazine bridge has high receptor affinity to mu, kappa, and delta receptor types, as well as potent and long acting antinociceptive activity after intraperitoneal administration.

The effect of enkephalin dimers on body temperature in mice.

Short-lasting decrease in rectal temperature in mice after intraperitoneal administration of an enkephalin dimer, the so called double-enkephalin--(Tyr-D-Ala-Gly-Phe-NH)2 (D-ENK-O)--at dose 0.1, 0.5, 1, 2.

The effect of food and water deprivation on post-stress analgesia in mice and levels of beta-endorphin and dynorphin in blood plasma and hypothalamus.

Pain sensitivity of food and/or water-deprived male mice was tested on a hotplate. The most pronounced analgesia ensued in animals given no food and water, and no food but water ad libitum, the least one in water-deprived mice. The magnitude of the rise in pain threshold depended on the duration of deprivation and was correlated with the increase in the blood plasma beta-endorphin level.

Suppression of food and water intake after intracerebroventricular infusion of morphine and naloxone in rabbits.

The effect of intracerebroventricular infusion of morphine and naloxone on food and water intake was investigated in rabbits. Morphine hydrochloride at a dose of 120, 10 and 5 micrograms produced statistically significant suppression of 24-h food and water intake. The same effect ensued after infusion of naloxone at dose of 120 and 10 micrograms.

Double-enkephalins--synthesis, activity on guinea-pig ileum, and analgesic effect.

We have synthesized enkephalin analogues in which C-terminal methionine or leucine residues are replaced by a second active fragment of the enkephalin analogue. Synthesis of two compounds is described: in one, two fragments of a D-Ala2-enkephalin analogue are connected by a -NH-NH-bridge, and in the other, three methylene groups are incorporated between the amino groups. The first compound is a very potent inhibitor of electrically induced contractions of guinea-pig ileum and produces a strong analgesia when administered intraperitoneally in mice.

The effect of intracerebroventricular infusion of morphine, methionine-enkephalin and D-Ala2-enkephalinamide on body temperature of rabbits.

The effect of intracerebroventricular infusions of two synthetically obtained peptides: Met-enkephalin hydrochloride and D-Ala2-Met-enkephalinamide hydrochloride, and of morphine hydrochloride on rectal temperature was investigated in conscious rabbits. Morphine hydrochloride in a dose of 240 micrograms and D-Ala2-Met-enkephalinamide hydrochloride in doses of 240 and 3000 micrograms produced a hyperthermia which was accompanied by ear vasoconstriction and shivering. No such effect ensued after Met-enkephalin, possibly due to rapid enzymatic degradation of this compound.