Expression of stress-evoked analgesia, connected with activity of animals in a forced swimming test]

The influence of forced swimming on the development of stress-induced analgesia was studied in 35 SHR mice, 65 NMRI mice, and 23 white outbred male rats. Mice were subjected to swimming conditions (at a temperature of 11 degrees C) for a period of 4 minutes and rats for 6 minutes. Pain thresholds were measured by a footshock. It was shown that behavioral response to acute stress is associated with a change in the pain tolerance threshold: activity of an animal under test conditions positively correlated with stress-induced analgesia. The response to stress and parameters of stress-induced analgesia depend on the genetic factor and age, however, the correlation between the activity during exposure to stress and the extent of stress-induced analgesia conserves in all cases.     

Role of the somatic monoaminergic systems in the mechanisms of regulation of pain sensitivity during reflex stimulation

Experiments on rats were performed to study the role of the monoaminergic systems in the mechanisms of analgesia produced by stress (foot shock) and auricular electroacupuncture (AEA). Analgesia was measured by the hot-plate (HP) and the tail-flick (TF) tests. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha-MPT) antagonized the AEA-induced analgesia measured by the TF test. alpha-MPT did not influence the HP test latency after AEA, and HP or TF tests after stress. Inhibition of dopamine receptors by haloperidol produced a decrease in the stress- and AEA-induced analgesia. The similar effects were demonstrated in propranolol treated rats after AEA. P-chlorophenylalanine (an inhibitor of serotonin synthesis) suppressed the stress-induced analgesia measured by the HP test and AEA-induced analgesia measured by the HP or TF tests. The data indicate that the monoaminergic systems are involved in the stress- and AEA-induced analgesia. Apart from the monoaminergic systems, other neurochemical mechanisms are also involved in the stress- and AEA-induced analgesia.     

Increases in plasma beta-endorphin and tail flick latency in the rat following burn injury

In children with burn injuries we found, in earlier studies, an inverse association of plasma beta-endorphin immunoactivity (iB-EP) and pain levels. To further explore the effects of burn trauma on the peripheral release of beta-endorphin and the occurrence of centrally mediated stress analgesia, plasma iB-EP levels and tail flick latency (TFL) were measured in rats subjected (while anesthetized) to scald injury. In comparison to sham burn (dip in tepid water), burn injury increased plasma iB-EP and TFL; both the duration and magnitude of these effects were directly proportional to the extent of burns. In rats receiving no treatment, TFLs were unchanged throughout the time of the burn experiments. At 2 days post-burn TFLs were invariably back to pre-burn levels. Administration of the long-acting opioid antagonist naltrexone prior to burn injury prevented the rise in TFL. Thus the trauma of burns appeared to bring about a stress-induced analgesia (SIA). The marked increase in iB-EP during this SIA and its antagonism by naltrexone suggest that it was opioid and hormonal in character.     

Naloxone hyperalgesia and stress-induced analgesia in rats

Since past studies concerning the effects of naloxone on nociception have yielded inconclusive findings, the variables of pain test, baseline sensitivity, and stress condition were examined. Within a pure-bred strain of rats, consistent individual differences did not occur. All three measures of pain responsiveness demonstrated hyperalgesic effects of naloxone, but they differed in their capacity to reflect the effects of analgesia produced by continuous or intermittent electrical shock. By some measures, naloxone reversed the stress-induced analgesia due to intermittent shock; it did not influence the analgesia produced by continuous stress. The data support a model of pain inhibition involving both opioid and non-opioid systems and suggest that the hyperalgesic effects of naloxone can sometime gives rise to erroneous conclusions concerning apparent naloxone-reversability of putative analgesic procedures.     

Inherent efficiency of stress-limiting systems as a factor of the resistance to stress-induced disorders

A hypothesis is substantiated in accordance to which a resistance of an organism to stress damages depends upon genetically determined peculiarities of its regulatory stress-limiting systems that restrict stress reaction and its detrimental effects. A comparison of differences between the stress resistance and the activity of the stress-limiting systems (dopaminergic, serotoninergic, nitric oxide and heat shock proteins systems) in rats of two strains August and Wistar indicates that the higher hereditary activity of mentioned systems is associated with the higher resistance to acute emotional stress; and the lower hereditary activity of these systems associated with the lower resistance to this stress. At the same time the adaptation to repeated non-damaging exposures to stressor aimed to rise the stress resistance leads to opposite results in rats of the mentioned strains. In the animals with the higher hereditary resistance to acute stress (August rats) the adaptation reduces this resistance. In the animals with the lower hereditary stress resistance (Wistar rats) that sort of adaptation really rises this resistance. That is determined by changes in activity of the stress-limiting systems during repeated stress exposures. In the animals with the higher hereditary activity of the stress-limiting systems the adaptation reduces the activity of these systems. In the animals with the lower hereditary activity of the stress-limiting systems the adaptation rises this activity and the resistance of these animals to stress damages.     

The selective role of the nucleus raphe magnus in the mechanisms of analgesia in electrocutaneous pain stimulation, cold stress and the action of morphine

Inhibition of the analgetic activity of systemic morphine and inescapable foot shock in certain moments of the experiment was shown on rats subjected to electrolytic destruction of nucleus raphe magnus. Cold swim stress increased analgesia as compared to the control animals. It is concluded that this formation of the brain is selectively and dynamically involved in mechanisms of various types of analgesia.     

Comparative analysis of the role of beta-endorphin systems in the mechanisms of different types of analgesia

Repeated immunization of rats with beta-endorphin-bovine albumin conjugate (75:7.5 g) mixed with Freund's adjuvant (1:1) induced a significant decrease in beta-endorphin content in the pituitary body and hypothalamus. The immunized rats showed suppressed antinociceptive reaction to morphine (5 mg/kg, i.p.) and in unavoidable foot shock. Cold swimming stress did not influence the pain reactions, as compared to the control group. The results indicate that mechanisms of different types of analgesia involve selective neurochemical systems.     

Effect of enkephalins on the function of the calcium-regulating endocrine glands in shock

The experiments on white rats weighing 180-220 g have shown that in traumatic and hemorrhagic shock the initial increase in parathyroid hormone blood concentration is followed by the decrease of functional activity of parathyroid glands. Calcitonin concentration is found to increase during the first hours of shock. The changes in calcium-regulating gland function result in significant disturbances of calcium exchange during shock. The injection of synthetic leu-enkephalin analogs to rats with shock leads to normalization of calcium-regulating endocrine glands function.     

beta-Endorphin controls vasopressin release during foot shock-induced stress in the rat

This study tested the possibility that beta-endorphin is involved in the regulation of vasopressin release during stress induced by inescapable electric foot shock. To this end, a specific anti-beta-endorphin antiserum or a control serum lacking the specific anti-beta-endorphin antibodies was administered to male rats. Plasma vasopressin concentrations, measured by radioimmunoassay, were not affected by brief foot shock stress in control rats, but were raised significantly by the stress in animals which had received an intracerebroventricular (i.c.v.) injection of the anti-beta-endorphin antiserum. In contrast, when the same volume of the anti-beta-endorphin antiserum was injected into a tail vein, foot shock stress produced only a slight effect on vasopressin release. I.c.v. injection of the antiserum changed neither basal nociceptive threshold nor stress-induced analgesia as revealed by the tail-flick latency. Vasopressin release induced by an osmotic stimulus was not influenced by the anti-beta-endorphin antiserum given i.c.v. The opiate antagonist naloxone or the glucocorticoid dexamethasone raised plasma vasopressin concentration in stressed rats which had received the control serum (i.c.v.); however, after i.c.v. injection of the anti-beta-endorphin antiserum neither naloxone nor dexamethasone elevated the plasma vasopressin concentration beyond the level reached by the anti-beta-endorphin antiserum (i.c.v.) alone. These results suggest that beta-endorphin inhibits the release of vasopressin during foot shock-induced stress in the rat.     

Effects of antibodies to lysosomal enzymes on the course of experimental burn shock]

On the model of burn shock in rats, the influence of antibodies to lysosomal enzymes has been studied in respect to the cathepsin D activity, oxygen regimen, acid-base equilibrium in blood, and animal survival. It has been shown that the antibodies inactivate the cathepsin D activity which is increased in burn shock. Because of the decreased cardiodepressant action of the lysosomal enzymes, the blood circulation improves, the manifestations of hypoxia and metabolic acidosis are attenuated. The results obtained confirm an important role of the lysosomal in the pathogenesis of bur, shock and permit one to consider its therapy using antibodies to the lysosomal enzymes to be promising.     

Effects of <Emphasis Type="SmallCaps">d</Emphasis>-kyotorphin on nociception and NADPH-d neurons in rat’s periaqueductal gray after immobilization stress

d-kyotorphin (d-Kyo) is a synthetic analogue of the neuropeptide kyotorphin and produces naloxone reversible analgesia. Stress-induced analgesia (SIA) is an in-built mammalian pain-suppression response that occurs during or following exposure to a stressful stimulus. The periaqueductal gray (PAG) is implicated as a critical site for processing strategies for coping with different types of stress and pain and NO affects its activity. The objectives of the present study were twofold: (1) to examine the effects of d-Kyo (5 mg/kg) on acute immobilization SIA; (2) to investigate the effect of peptide on NO activity in rat PAG after the stress procedure mentioned above. All drugs were injected intraperitoneally in male Wistar rats. The nociception was measured by the paw pressure and hot plate tests. A histochemical procedure for nicotinamide adenine dinucleotide phosphate–diaphorase (NADPH-d)-reactive neurons was used as indirect marker of NO activity. Our results revealed that d-Kyo has modulating effects on acute immobilization stress-induced analgesia in rats may be by opioid and non-opioid systems. Although d-Kyo is incapable of crossing the blood–brain barrier it showed an increased number of NADPH-d reactive neurons in dorsolateral periaqueductal gray (dlPAG) in control but not in stressed groups. We may speculate that the effect of d-Kyo in the brain is due to structural and functional interaction between opioidergic and NO-ergic systems or d-Kyo appears itself as a stressor. Further studies are needed to clarify the exact mechanisms of its action.     

Early evolution of selenium status and oxidative stress parameters in rat models of thermal injury

The objective of the present study was to measure the relationship between selenium status and oxidative stress in two rat models of thermal injury. A non-lethal third-degree burn injury involving 20% (experiment 1) or 40% (experiment 2) of total body surface area (TBSA) was applied to male Wistar rats. Selenium level, glutathione peroxidase (GPx) activity in plasma, red blood cells (RBC) and tissues (liver, kidney, muscle, and brain), and plasma selenoalbumin (Se-alb) were measured in control rats and in burned rats respectively 6 hours after injury and daily from day 1 to day 5. In parallel, lipid and protein oxidative damages, monitored by plasma and tissue thiobarbituric acid reactive species (TBARs) levels and plasma total thiol groups were assessed.

We observed a decrease of plasma Se and Se-albumin 6 hours after burn injury. In parallel, plasma GPx activity rapidly decreased and remained significantly lower than in control rats. These alterations were enhanced by the burn injury severity. Plasma TBARs followed the same pattern as that of plasma cholesterol, with an initial decrease and an increase at day 3 in 40% TBSA burned rats. Plasma thiol groups decreased in the two experiments indicating plasma protein oxidation.

These results confirm an early oxidative stress in burn injury, and suggest an early selenium mobilization, which might counteract this oxidative stress. These data underline the crucial need of a restored selenium status in burned patients immediately after the burn injury.     

Potentiation of foot shock analgesia by thyrotropin releasing hormone

Thyrotropin releasing hormone (TRH) interacts with both opioid and non-opioid systems in mediating hypothermic, hypoactive, cataleptic, respiratory and analgesic effects. While TRH neither antagonizes opioid analgesia nor alters pain thresholds itself, it blocks neurotensin analgesia. Different forms of pain-inhibition in rats can be activated by selectively altering the parameters of shock: while analgesia induced by 20 inescapable tail-shocks is not reversed by naltrexone, exposure to 60 or 80 shocks does elicit naltrexone-reversible analgesia. The first experiment examined whether intracerebroventricular administration of TRH (0, 10, or 50 micrograms) would alter the elevations in tail-flick latencies in rats induced by 20 or 80 foot shocks and found that TRH significantly lengthened the duration and magnitude of analgesia induced by 20 and 80 foot shocks in a dose-dependent manner. The second experiment extended these findings to the writhing test, a visceral pain test. While the number and duration of writhes of vehicle-treated rats exposed to 80 foot shocks failed to differ from baseline values. TRH (50 micrograms)-treated rats exposed to 80 foot shocks displayed significant decreases in the number and duration of writhes. The third experiment indicated that the differential effects of naltrexone upon analgesia induced by 20 or 80 tail shocks were not apparent when foot shocks were employed, precluding a definitive statement that TRH may be involved in the modulation of both opioid and non-opioid forms of analgesia.     

Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock

Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.     

Analysis of analgesia induced by the generator of excitation in the dorsal raphe nucleus

In experiments on white rats the generator of excitation was created in the dorsal raphe nucleus by microinjection of tetanus toxin. After formation of the excitation generator electrical activity in this nucleus was changed as the following: the first negative component (N1) was strongly increased, general EP configuration changed and the spontaneous paroxysmal activity became more frequent. The time of the generator formation correlated with the appearance of intense and prolonged analgesia. Naloxone did not reverse the effects of analgesia described.     

Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats

The present study was designed to determine whether exogenous leptin reduces remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg) or saline was administered intraperitoneally after burn injury, and the rats were decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed for the determination of monocyte and neutrophil apoptosis. Thermal injury increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn groups. In the 6-h burn group, leptin reduced microscopic damage score in the liver and kidney only, while damage scores in the 24-h burn group were reduced in all the tissues except the lung. Also, in both burn groups, leptin reduced elevated MPO activity in all tissues except the lung. The percentage of mononuclear cells was significantly reduced at the 24 h of burn injury, while the granulocyte percentage was increased. Leptin treatment, however, had no significant effect on burn-induced reversal of white blood cell ratios. On the other hand, burn-induced increase in the death of mononuclear cells and granulocytes was significantly reduced in leptin-treated rats. The results of the present study suggest that leptin may provide a therapeutic benefit in diminishing burn-induced inflammation and associated multiple organ failure.     

Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation

The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin.     

纳洛酮对大鼠烫伤休克的影响

36只烫伤大鼠,分为纳洛酮组和盐水对照组。两组动物侧脑室分别注射纳洛酮和生理盐水,观察纳洛酮对烫伤休克的影响。 结果表明:纳洛酮组大鼠的存活率高于盐水对照组。纳洛酮组动物烫伤后2小时存活率为83％,烫伤后4小时存活率为39％;盐水组动物烫伤后2小时存活率为44％,烫伤后4小时存活率为5.6％。纳洛酮组血压下降和心率减慢的进度也较慢,烫伤后180分钟血压才降低到63％,而盐水组在烫伤后90分钟血压已降低到62％。纳洛酮组动物的呼吸和体温变化也较慢。这些结果提示:纳洛酮具有一定的抗烫伤休克的作用。     

Peroxidase activity in non-embryogenic and embryogenic calli and in developing somatic embryos of white fir (Abies concolor Gord. et Glend)

ABSTRACT

Peroxidase activity was monitored during somatic embryogenesis of white fir (Abies concolor Gord. et Glend) starting from a non-embryogenic callus. Results revealed profound differences between non-embryogenic and embryogenic calli with an elevated level of enzyme activity in non-embryogenic ones. Precotyledonary, early cotyledonary and late cotyledonary stages of somatic embryogenesis were characterized by a substantially reduced peroxidase activity compared to callus tissues and regenerated plantlets. Changes in peroxidase activity are as a rule paralleled by variation in isoenzyme composition. The utility of the enzyme in the induction stage of somatic embryogenesis in white fir is proposed.     

Comparative study of intravital microcirculation and hemorheological changes following burn injury of different severity in rats

It was shown in experiments on rats that burn injury is followed by microcirculatory disturbances, hemoconcentration and increasing blood viscosity that is especially pronounced in the vessels with low blood pressure. The microcirculatory changes in the mesentery correlated with the in vitro investigated dynamic viscosity and blood composition. The disturbances were more pronounced after severe burn followed by a mortal shock than after moderate burn without fatal consequences. This investigation confirms great importance of hemorheological changes and microcirculatory disturbances in the early period of burn disease.