Antinociceptive effect of the agonist of 5-HT1A receptors buspirone in the model of abdominal pain in dogs.

We have demonstrated that activation of 5-HT1A receptors with buspirone promotes visceral analgesia in awake dogs. The administration of 0.035 mg/kg (i.m.) of the drug caused depression of viscero-motor (contraction of the abdominal muscles) and pressor (increase in the heart rate) responses to noxious distension of the large intestine. An increase in the dose to 0.07 and 0.14 mg/kg did not enhance the antinociceptive effect of buspirone but triggered basal tachycardia. The obtained results provide evidence of the inhibitory role of 5-HT1A receptors in modulating visceral pain sensitivity and the possibility of an exciting effect of their activation on the cardiovascular system.

[Changes in the intragastric contents during sleep affect the statistical characteristics of the neuronal activity in cerebral cortex].

Firing activity in somatosensory cortical area was analyzed in cats during slow wave sleep. Statistical characteristics of the background activity were calculated before and after changes of the intragastric contents (introduction of 50 ml of water into stomach). This procedure did not affect the depth of sleep. There were no changes of the mean firing frequency and the local variation coefficients. To evaluate the degree of chaos in neuronal firing before and after changes of the intragastric contents, the dependence of the Fano factor from the length of the intervals of analysis was calculated. This dependence before water infusion for 40 neurons expressed as a power function with index of power > 0.2 what indicated on fractal nature of the background activity. The changes of the gastric contents in 18 neurons lead to considerable changes of the indexes of power of this function. It is known that in wakefulness for cortical neurons these indexes are dependent on the specific sensory stimulation. Thus, our results can be considered as an indication that during slow wave sleep signals from stomach are included in the afferent flow to the cortical areas, which in wakefulness are involved in somatosensory functions.

[The effects of selective 5HT3 receptor blockade on physiological markers of abdominal pain in awake dogs].

In awake dogs, the visceromotor and cardioautonomic responses to the rectal balloon distension were studied before and after intravenous administration of a selective 5HT3 receptor antagonist granisetron. It was shown that balloon distension level up to 60 mmHg caused neither noticeable muscle responses nor substantial changes in heart rate. In turn, distending pressures of 80 mmHg and higher induced vigorous abdominal muscle contractions and tachycardia that were graded with increasing intensities of stimulation. Thus, the rectal stimulation with pressures 80 mmHg and more produced the changes in visceromotor and cardiovascular indices which could be considered as suitable indicators of visceral nociception in conscious animals. Based on monitoring of these physiological markers in a model of abdominal pain the dose-dependent antinociceptive effect of granisetron in awake dogs has been demonstrated for the first time. It was determined that granisetron in doses of 0.25, 0.5 or 1.0 mg/kg induced correspondingly 33.6 +/- 9.2, 58.0+/- 8.6 [see text] 76.7 +/- 5.5 % decrease in visceromotor response of dogs to nociceptive visceral stimulation. The effect occurred immediately after the drug administration and was lasting more than 90 min. In turn, the dose-dependent suppression of the rectal distension-induced tachycardia was less prominent and only observed during the initial period of granisetron action. The described model of abdominal pain in awake dogs might be useful for preclinical screening of new pharmacological substances, whereas the obtained data could contribute to the development of more efficient analgesics aimed in patients with irritable bowel syndrome.

Effects of stimulation of the insular cortex on execution of the antrofundal reflex in conscious dogs.

Neuroanatomical studies demonstrated the existence of direct descending projections from the insular cortex to the area of the solitary tract nucleus responsible for mediating the vagovagal reflexes of the proximal part of the gastrointestinal tract. These studies provided grounds for suggesting that one of the mechanisms mediating the influences of the insular cortex on stomach function may be modulation of its vagovagal reflex reactions, one of which is the antrofundal inhibitory reflex. Experiments on conscious dogs were performed to study the effects of electrical stimulation of the insular cortex on execution of the antrofundal gastric reflex in conditions of intermittent gastrointestinal tract activity during fasting. Stretching of the walls of the antral segment of the stomach during the active period of intermittent gastric activity led to suppression of contractions in the fundal segment. Electrical stimulation of the insular cortex was found to prolong this reflex reaction. Thus, one result of activation of the insular area of the cortex is enhancement of the inhibitory vagovagal gastric reflexes, in all probability occurring as a result of modulation of neurotransmission in the vagovagal reflex arc system.

[Effects of the insular cortex stimulation upon realization of the antro-fundal gastric reflex in alert dogs].

Neuroanatomic studies demonstrate direct descending projections from the insular cortex to the gastric area of the solitary tract nucleus. This allows us to hypothesize that the insular cortex is able to modulate vago-vagal gastric motor reflexes such as antro-fundal inhibitory reflex. In experiments on conscious dogs demonstrating fasting gastric motility, the effects of electrical stimulation of the insular cortex upon realization of the gastric antro-fundal reflex were studied. Distension of the antrum applied during active period of gastric motility inhibited contractions of the fundus. Electrical stimulation of the insular cortex did not affect the time pattern of fasting gastric motility but resulted in significant prolongation of the antro-fundal reflex. Thus, activation of the insular cortex leads to augmentation of gastric vago-vagal inhibitory reflex. The effect may be realized due to corticofugal modulation ofvago-vagal neurotransmission within the nucleus of the solitary tract.

[The neurons of the medial vestibular nucleus initiating the relaxation of the rat's stomach wall]. / Neirony medial'nogo vestibuliarnogo iadra, initsiiruiushchie relaksatsiiu stenki zheludka u krys.

In acute rat experiments the technique of retrograde axonal transport of horseradish peroxidase in the medial vestibular nucleus allowed to identify a group of neurones sending axons to the "stomach" region of a single tract nucleus. These neurones and, accordingly, the descending vestibular/solitary links can be viewed as the morphologic basis for vestibular influences on the gastric motor activity. As was shown, local irritation of the neurones initiates relaxation of the stomach wall. Activation of the anterior limbic cortex modulates the vestibular/autonomous responses of the intragastric pressure reduction. Irritation of the infralimbic cortex of the rat's brain may have a preventive effect on the stomach wall relaxation stimulated by the vestibular neurones projecting on the "stomach" region of single tract nucleus.

[Interdigestive stomach motor activity in dogs during stimulation of the duodenal receptors by sodium oleate]. / Mezhpishchevaritel'naia motornaia aktivnost' zheludka u sobak pri stimuliatsii retseptorov dvenadtsatiperstnoi kishki oleatom natriia.

Administration of 20% sodium oleate solution in the duodenum of awake dogs suppresses stomach contractions and decreases duration of the postprandial motor complex. Benzohexonium eliminates these oleate effects. The findings suggest that the oleate activates cholinergic vago-vagal reflex which modifies the postprandial motor complex.

[The effect of microinjections of bombesin into the amygdala on the slow-wave frequency of the gastroduodenal smooth muscles and on the migrating myoelectric complex]. / Vliianie mikroin''ektsii bombezina v mindalinu na chastotu medlennykh voln gladkikh myshts gastroduodenal'noi zony i migriruiushchii mioélektricheskii kompleks.

In dogs with electrodes implanted in the smooth muscle wall of the stomach and duodenum, microinjection of bombesin (5 micrograms) during the 2nd phase of the migrating myoelectric complex decreased frequency of slow waves in the stomach, leaving unaltered the frequency of slow waves in the duodenum. Bombesin caused a short-term inhibition of the gastric and intestinal spike activity followed by its increase, the active period of the migrating myoelectric complex being prolonged.