Annals of Burns and Fire Disasters - vol. XI - n. 3 - September 1998

STRESS ANALGESIA ASSOCIATED WITH EXPERIMENTAL BURN SHOCK

Sinitsin L. N.

Research Institute of Traumatoiogy and Orthopaedics, Ministry of Health, Nizhniy Novgorod, Russia

SUMMARY. This paper considers excitation transmission changes in the afferent and visceral efferent cerebral systems, the threshold of pain sensitivity, the endogenous opiate synthesis level, and the character of the antishock agent activity due to burn shock.

Introduction

Experiments with curarized and moderately anaesthetized adult cats with burn shock have demonstrated a pronounced depression of excitation transmission in the associative and nonspecific afferent systems during somatic, sound and light stimulation. The effects controlling the activity of the cardioavascular system are facilitated in the efferent systems. In white rats, burn shock leads to an increase in the somatic and visceral pain threshold during the first five days. Rausedyl and naloxone reduces stress analgesia caused by the burn shock in white rats. The burn shock enhances opiate-like activity (beta-endorphin, beta-lipotropin) of the white rat forebrain, as shown by radioimmunoassay. The data suggest that stress analgesia associated with experimental burn shock is likely to be accounted for by the increased production of endogenous opiates.
CNS disturbances due to the burn shock are well known.' However, the peculiarities of excitation transmission changes in cerebral structures due to shock of various aetiology have not been well investigated. This matter has recently aroused great interest owing to the development of the endogenous opiate theory, according to which the vital activity products of the brain regulate its excitability and influence impulse transmission, causing stress analgesia in extreme conditions.
The present study investigates excitation transmission changes in the afferent and visceral efferent cerebral systems, the threshold of pain sensitivity, the endogenous opiate synthesis level, and the character of the antishock agents activity due to burn shock.

Methods

The experiments were carried out on 50 adult cats and 300 intact rats. The cats were anaesthetized with chloralose (10-30 mg/kg) and immobilized with succinylcholine, with artificial ventilation control and body temperature within the norm.
The influence of the damaging factors on the excitation transmission in the afferent systems was investigated with the method of the registration of evoked potentials in specific associative and non-specific structures of the cerebral hemisphere cortex, the diencephalon and the mesencephalon, due to somatic, sound and light stimulation.
The evoked potentials were recorded by means of a 6channel "Alvar" amplifier and a 6-channel cathode-ray oscillograph, using the waiting/scanning system of multiple superposition on the film. The sciatic nerve was stimulated with single or double I msec square wave impulses at I imp/sec frequency. Sound and light impulses were received with corresponding transformations of the electric impulses.
The influence of burn trauma on the excitement transmission in the efferent visceral systems was investigated under the same conditions with the method of local electrical stimulation of the sensorimotor zone of the cerebral hemisphere cortex, diencephalon and midbrain structures and recording of neurogenous arrhythmia, hypertension reactions, and changes in the general level of arterial blood pressure. ECG in the second standard conduction and arterial blood pressure in the femoral artery were recorded, by means of "Cardiovar" and "Bariovar" (manufactured by Alvar). The brain was stimulated with 1 msec square wave electrical pulses of 5-10 V amplitude with 200 imp/sec frequency at 5 sec intervals.
A third-degree burn shock (a-b) was inflicted in 20-30% of the total body by contact burn using a metal plate heated to 100°C.

Results

The results of the experiments showed that some relief of the excitement transmission in the afferent system appeared during the first hours after the infliction of the burn trauma in the animals. The amplitude of the primary responses was enlarged by somatic, sound and light stimulation in the fields of specific projection in the cerebral cortex. In the associative and non-specific fields, the amplitude and the length of responses increased in conditions of sound and light stimulation. On the level of the diencephalon and midbrain, in the associative and nonspecific thalamus nuclei, the hypothalamus and the reticular formation structures, the increase in amplitude of the evoked potentials was observed to be less expressed by somatic stimulation and more markedly increased by sound and light stimulation. Starting from the second hour, the relief in excitation transmission modified to suppression, which increased constantly and reached its maximum at the end of the first 24 h. This was manifested in decreased amplitude and increased latent period and evoked potential length. The responses in the associative and non-specific areas of the cerebral cortex were more suppressed and the primary responses in the fields of specific projection were less suppressed (Fig. 1). In the experiments with double pulses the responses to the second impulse were mostly suppressed, which testified to decreased liability of the brain afferent systems.

Analogous changes in excitation transmission were observed in the associative and nonspecific structures of the diencephalon and midbrain. In response to sciatic nerve sound and light stimuli, the amplitude of the evoked potentials decreased, and their latent period and length increased. Acute depression of the potentials was observed at the end of the first 24 It (Fig. 2).

In the efferent systems the burn trauma caused an acute increase in the decreased effects controlling the activity of the cardiovascular system. The general level of arterial blood pressure increased on average by 18 % during the first hours. Hypertension was maintained in most of the experiments during the first 24 h, which was followed by and a decrease in the general level of arterial blood pressure to initial and lower values.
Hypertensive reactions and the stimulation of the sensorimotor areas of the cerebral cortex nonspecific stiruclures of the diencephalon and midbrain increased on average after burn infliction by 81% as compared with the initial values and remained at that level during the first 24 h, after which their intensity gradually decreased.
The continuity of neurogenic arrhythmias resulting from the local stimulation of the cerebral structures in question increased in 3.7 times during the first 2 h postburn. This effect gradually decreased but persisted for the first 24 h.

Discussion

A comparative analysis of the data allowed us to hypothesize that the burn shock caused changes in excitation transmission in the afferent and efferent brain systems analogous to those observed following by the action of narcotic analgesics of the morphine group.` These assumptions formed the basis for further experiments in which the influence of the burn shock on somatic and visceral pain sensibility was studied.
The experiments were carried out on white rats weighing 150-200 g. The pain thresholds were determined with the previously developed method of somatovisceral analgesiometry.` After immobilization the animals received stimulating bipolar electrodes in the upper third of the tail and abdomen. Stimulation was carried out with 1 msec square wave pulses in packets (10 impulses per packet) at 5 see intervals. The pain threshold value was determined by the power value of the stimulating pulse curve causing motor reaction, squeaking during stimulation, and squeaking after stimulation. The stimulating current power was measured with a Cl-19 cathode oscillographer by the tension drop on the resistor switched on consecutively with the object.
The results showed that 1 h post-burn there was an increase in the somatic and visceral pain sensibility threshold. This gradually increased and reached its maximum level by the end of the first 24 h, 5-10 times higher than the initial level. The somatic pain threshold increased in this period more than the visceral threshold. During the following five days the pain thresholds gradually decreased to initial values.
These data made it possible to assume that the burn trauma caused stress analgesia in animals which, according to reports, 2-6 was the result of the hyperproduction of endogenous opiates in the brain structures. To confirm this assumption, we determined the total opiate-like activity (beta-endorphin, beta-lipotropin) of the anterior cerebral areas of white rats due to the burn trauma. The investigation was carried out using N-Nuclear Corporation radio-immune diagnostic sets (USA). Radioactivity was determined by automatic LKB gamma counter (Sweden).
It was established that in the control group of the intact rats the total opiate-like activity was 121.64 ± 11.9 pm/mg, while in white rats killed 24 h after burn infliction the opiate-like activity was 199.5 ± 21.6% pm/mg. The results of the experiments testified to the fact that the burn shock caused opiate-like activity enchancement as compared with the control values at 75.5 pm/mg in 2 h and 77.55 pm/ing in 24 h post-burn trauma (p < 0.05) (Fig. 3).

On the basis of these experimental data, we can state that in conditions of experimental hum shock there was evident stress analgesia resulting from increased production of endogenous opiates.
For further analysis of the stress analgesia mechanism due to burn shock, we used this model to study the effect of the antagonist agents of the endogenous opiates - naloxone, rausedyl` and their synergists (narcotic analgesics and enkephalin derivatives) on pain threshold changes in burned animals.
The results showed that rausedyl in doses of 20 mg/kg reduced the increase of the pain thresholds of somatic and visceral pain sensibility due to burn shock. Under the same conditions (5 mg/kg) naloxone also reduced the post-burn increase of the pain threshold. Action was manifested 10 min after administration and lasted for 1 h. On the second day the pain thresholds were sharply decreased compared with animals not receiving naloxone (Fig. 4).
Analgesics were administered to white rats before and 10, 30, 60 and 120 min after infliction of burn trauma, as also after 24-48 h. Morphine (10 mg/kg), phentanyl (10 mk/kg) and lexir (1 mg/kg) administered 2-3 h after the burn trauma were found to cause a sharp increase of the pain threshold in comparison with both burned and intact animals. In the latter case, the somatic pain threshold increased respectively 10, 3 and 4 times and the visceral pain threshold 1.5, 4 and 5 times. The administration of 200 mg/kg gamma-OH produced a similar effect.

Fig. 4  - Influence of naloxone on visceral stress analgesia due to experimental burn shock in white rats. Ordinate axis: pain threshold values (in cond. units). Initial pain threshold on basis of vocalization reaction after stimulation is considered as follows: a - within 2 min of burn infliction; b - within 10 min; c - within 30 min; d - within 60 min; e - within 2 h; f - within 24 h of naxolone administration at dose of 5 mg/kg. Light columns - control animals, receiving sodium chloride solution; Shaded columns - animal receiving naloxone (10 rats per group). Vertical lines indicate confidence limits.

The same doses of the drugs applied before or 10, 30 and 60 min after burn application were also found to prevent further increase of the pain threshold after termination of action. After 24 h the pain thresholds in animals that had received analgesics before or for 1 after the burn trauma were 3-5 times lower in comparison with the burned animals in the control group. 
The experimental results testify that stress analgesia develops, followed by burn shock, as a result of hyperproduction of endogenous opiates. These potentiate the analgesic effect of the opiates if the opiates are applied 2 h after the burn trauma or later. Also, the administration of narcotic analgesics, either preliminarily or for 1 h, can prevent initiation of the hyperproduction of endogenous opiates, which is a factor of their antishock effect. Separately we show that ley-enkephaline administration to the brain ventricles of white rats (1 ing in 5 ml) resulted in the acute increase of the somatic and visceral sensibility pain thresholds. This demonstrated the role of endogenous opiates in the development of central analgesic action.

Conclusions

The results of the investigations testify that excitation transmission in the afferent and efferent cerebral systems significantly changed in conditions of extreme shock. This led to a modification in the action of neurotropic agents applied in anaesthesiology in order to prevent and treat burn shock. The character of the neurotropic agent action varied in relation to the phase and the degree of the shock. These factors should be taken into consideration in clinical practice in order to provide more rational and effective correction of disturbances of the central nervous system in shock conditions.

RESUME. L'Auteur considère les modifications de la transmission de l'excitation des systèmes cérébraux afférent et efférent, le seuil de la sensibilité à la douleur, le niveau de la synthèse de l'opiacé endogène, et le caractère de l'activité des agents antichoc due au choc de la brûlure.

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