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Various behavioural nociceptive reactions and individual resistance against stress were studied under conditions of stimulation of the immune processes by various techniques. The research problems included a study of influence of the immune stimulation with preparation "Imunofan" upon pain responses depending on individual resistance of animals to a stress, and the obtained results were compared with similar data in natural model of immune activation. To reveal central immune regulation of nociceptive reactions, imunofan was injected into brain ventricles. The work was carried out in 43 "Wistar" adult male rats. Free "open field" behaviour of animals was recorded to define a stress-resistance. Following nociceptive reactions, tail-flick to thermal stimuli; start, escape, jumping and vocalization to electrical skin stimulation, were studied. It was shown that intramuscular injection of imunofan (0.01 ml, 0.005% solution) depressed an active behaviour of animals in open field and reduced pain thresholds. This hyperalgesia was much higher in non-resistant rats in comparison to the resistant ones. Similar results were obtained in natural activation of immunity caused by operative procedure necessary for injection of imunofan into ventricles. Intracerebroventricular injections were accompanied by stronger and more complex changes of pain sensitivity.

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Tactile and pain thresholds were determined in 116 patients 24 hours before surgery upon premedication and administration of fentanyl and droperidol during induction to anesthesia. Statistical correlation analysis has shown that high pain thresholds in patients 24 hours before surgery indicate low consumption of barbiturates during induction to anesthesia, high efficacy of drugs used for NLA, and infrequent reactions to intubation irrespective of the efficacy of premedication. Low pain thresholds after premedication predict low efficacy of drugs for NLA and high consumption of fentanyl during surgery.

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The possibility of formation of some liposomal neurotropic drugs was studied by 1H-NMR method. Experiments in animals on catalepsy and epidural anaesthesia confirmed this hypothesis.

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It was found that chlorpromazine and pipolfene potentiating general anaesthesia increase viscosity of phospholipid membrane in the region of polar headgroups and in the hydrophobic area near glycerol sceleton. These results (independently of potentiating mechanism) confuse a mechanism of anaesthetics action as increased fluidity of membrane phospholipids.

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Experimental and clinical studies of the agent Piladox (RGH 2202) were conducted. Experiments on animals (rats, rabbits, mice) demonstrated that Piladox possesses the property of restoring respiration inhibited by narcotic analgesics and some general anesthetics as well as the respiratory-de-priming effect of acute blood loss and is a more effective stimulator of the respiratory center than cordiamine (nikethamide) or corasol. Clinical study of Piladox in 75 patients showed that intravenous infusion of 1 mg/kg of the agent in the awakening period produced a stimulating effect on respiration through increase of its frequency and increase of the respiratory volume. The minute respiratory volume in this case was even greater than the initial values, whereas the CO2 content in the blood and expired air reached the initial level. The hemodynamic values in this period remained generally stable. Piladox does not change the antinociceptive effect of the narcotic analgesics and analgesia in the immediate postoperative period when combined general anesthesia is applied.

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The effect of an thyroliberin analogue RGH 2202 on respiration inhibition induced by narcotic analgetics and on their antinociceptive action was studied in experiments on mice, rabbits and rats. RGH 2202 (10 mg/kg, intravenously) was found to exert no effect on the antinociceptive effect of morphine in mice and rabbits. Meanwhile, RGH 2202 in doses of 1 to 5 mg/kg intravenously abolished the respiration inhibition induced by fentanyl (0.02-0.07 mg/kg, intravenously) or morphine (10 mg/kg, intravenously) in rabbits and rats. After administration of RGH 2202 in doses of 10-40 mg/kg intravenously no significant changes of arterial blood pressure or heart rate were observed. The results obtained suggest that RGH 2202 may be used for relieving the inhibitory effects of narcotic analgetics on the respiratory centre during intoxication with these agents and in anesthesiological practice.

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The analgetic effect of prolonged peridural analgesia with morphine was studied experimentally in rabbits. Increasing morphine dose did not noticeably enhance analgesia. Prolonged peridural analgesia with morphine was used to alleviate pain in 18 myocardial infarction patients. Morphine (2 mg) was introduced into the peridural space. The efficacy of the method is demonstrated.

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Experimental studies conducted on rabbits enabled the authors to reveal the central mechanism of the ketamine effect. Based on the experimental data obtained, the authors elaborated and used clinically the method of balance ketamine anesthesia consisting in a combination of ketamine with antispasmatic drugs: seduxen and mydocalm. This method of anesthesia is recommended for eliminating ketamine side effects.

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