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Brain-cells as a Result of Trauma of Various Parts of the Body under Inhalation Anesthesia Numerous experiments on animals to determine the effect of ether anesthesia per se, i. e., ether anesthesia without trauma, showed that, although certain changes were produced, these included neither the physiologic exhaustion nor the alterations in the brain-cells which are characteristic of the effects of trauma.

On turning to the study of trauma, we at once found in the behavior of individuals as a whole under deep and under light anesthesia the clue to the cause of the discharge of energy, of the consequent physiologic exhaustion, and of the morphologic changes in the brain-cells.

 

If, in the course of abdominal operations, rough manipulations of the parietal peritoneum be made, there will be frequently observed a marked increase in the respiratory rate and an increase in the expiratory force which may be marked by the production of an audible expiratory groan. Under light ether anesthesia, severe manipulations of the peritoneum often cause such vigorous contractions of the abdominal muscles that the operator is greatly hindered in his work.

 

Among the unconscious responses to trauma under ether anesthesia are purposeless moving, the withdrawal of the injured part, and, if the anesthesia be sufficiently light and the trauma sufficiently strong, there may be an effort toward escape from the injury.

In injury under ether anesthesia every grade of response may be seen, from the slightest change in the respiration or in the blood-pressure to a vigorous defensive struggle. As to the purpose of these subconscious movements in response to injury, there can be no doubt—

THEY ARE EFFORTS TO ESCAPE FROM THE INJURY.

 

Picture what would be the result of a formidable abdominal operation extending over a period of half an hour or more on an unanesthetized human patient, during which extensive adhesions had been broken up, or a large tumor dislodged from its bed! In such a case, would not the nervous system discharge its energy to the utmost in efforts to escape from the injury, and would not the patient suffer complete exhaustion? If the traumata under inhalation anesthesia are sufficiently strong and are repeated in sufficient numbers, the brain-cells are finally deprived of their dischargeable nervous energy and become exhausted just as exhaustion follows such strenuous and prolonged muscular exertion as is seen in endurance tests.

Whether the energy of the brain be discharged by injury under anesthesia or by ordinary muscular exertion, identical morphologic changes are seen in the nerve-cells. In shock from injury (Fig. 2), in exhaustion from overwork (Hodge and Dolley) (Fig. 4), and in exhaustion from pure fear (Fig. 5), the resultant general functional weakness is similar—

in each case a certain length of time is required to effect recovery, and in each there are morphologic changes in the brain-cells. It is quite clear that in each of these cases the altered function and form of the brain-cells are due to an *excessive discharge of nervous energy. This brings us to the next question: What determines the discharge of energy as a result of trauma with or without inhalation anesthesia?

 

The Cause of the Discharge of Nervous Energy as a Result of Trauma under Inhalation Anesthesia and under Normal Conditions I looked into this problem from many viewpoints and there seemed to be no solution until it occurred to me to seek the explanation in certain of the postulates which make up the doctrine of evolution.

I realize fully the difficulty and the danger in attempting to reach the generalization which I shall make later and in the hypothesis I shall propose, for there is, of course, no direct final proof of the truth of even the doctrine of evolution.

It is idle to consider any experimental research into the cause of phenomena that have developed by natural selection during millions of years. Nature herself has made the experiments on a world-wide scale and the data are before us for interpretation.

Darwin could do no more than to collect all available facts and then to frame the hypothesis by which the facts were best harmonized.

Sherrington, that masterly physiologist, in his volume entitled “The Integrative Action of the Nervous System,” shows clearly how the central nervous system was built up in the process of evolution.

Sherrington has made free use of Darwin’s doctrine in explaining physiologic functions, just as anatomists have extensively utilized it in the explanation of the genesis of anatomic forms.

I shall assume, therefore, that the discharge of nervous energy is accomplished by the application of the laws of inheritance and association, and I conclude that this hypothesis will explain many clinical phenomena.

I shall now present such evidence in favor of this hypothesis as time and my limitations will admit, after which I shall point out certain clinical facts that may be explained by this hypothesis.

 

According to the doctrine of evolution, every function owes its origin to natural selection in the struggle for existence.

In the lower and simpler forms of animal life, indeed, in our human progenitors as well, existence depended principally upon the success with which three great purposes were achieved: (1) Self-defense against or escape from enemies; (2) the acquisition of food; and (3) procreation; and these were virtually the only purposes for which nervous energy was discharged. In its last analysis, in a biologic sense, this statement holds true of man today.

Disregarding for the present the expenditure of energy for procuring food and for procreation, let us consider the discharge of energy for self-preservation. The mechanisms for self-defense which we now possess were developed in the course of vast periods of time through innumerable intermediary stages from those possessed by the lowest forms of life. One would suppose, therefore, that we must now be in possession of mechanisms which still discharge energy on adequate stimulation, but which are not suited to our present needs.

We shall point out some examples of such unnecessary mechanisms.

As Sherrington has stated, our skin, in which are implanted many receptors for receiving specific stimuli which are transmitted to the brain, is interposed between ourselves and the environment in which we are immersed. When these stimuli reach the brain, there is a specific response, principally in the form of muscular action. Now, each receptor can be adequately stimulated only by the particular factor or factors in the environment which created the necessity for the existence of that receptor.

Thus there have arisen receptors for touch, for temperature, for pain, etc. The receptors for pain have been designated nociceptors

(nocuous or harmful) by Sherrington.

 

On the basis of natural selection, nociceptors could have developed in only those regions of the body which have been exposed to injury during long periods of time. On this ground the finger, because it is exposed, should have many nociceptors, while the brain, though the most important organ of the body, should have no nociceptors because, during a vast period of time, it has been protected by a skull.

Realizing that this point is a crucial one, Dr. Sloan and I made a series of careful experiments. The cerebral hemispheres of dogs were exposed by removing the skull and dura under ether and local anesthesia.

Then various portions of the hemispheres were slowly but completely destroyed by rubbing them with pieces of gauze.

In some instances a hemisphere was destroyed by burning.

In no case was there more than a slight response of the centers governing circulation and respiration, and no morphologic change was noted in an histologic study of the brain-cells of the uninjured hemisphere.

The experiment was as completely negative as were the experiments on the “spinal dog.” Clinically I have confirmed these experimental findings when I have explored the brains of conscious patients with a probe to determine the presence of brain tumors.

Such explorations elicited neither pain nor any evidence of altered physiologic functions. The brain, therefore, contains no mechanism—

no nociceptors—the direct stimulation of which can cause a discharge of nervous energy in a self-defensive action.

That is to say, direct injury of the brain can cause no purposeful nerve-muscular action, while direct injury of the finger does cause purposeful nerve-muscular action. In like manner, the deeper portions of the spinal region have been sheltered from trauma and they, too, show but little power of causing a discharge of nervous energy on receiving trauma. The various tissues and organs of the body are differently endowed with injury receptors—the nociceptors of Sherrington. The abdomen and chest when traumatized stand first in their facility for causing the discharge of nervous energy, _i.

e_., THEY STAND FIRST IN SHOCK PRODUCTION. Then follow the extremities, the neck, and the back. It is an interesting fact also that different types of trauma elicit different responses as far as the consequent discharge of energy is concerned.

 

Because it is such a commonplace observation, one scarcely realizes the importance of the fact that clean-cut wounds inflicted by a razor-like knife cause the least reaction, while a tearing, crushing trauma causes the greatest response. It is a suggestive fact that the greatest shock is produced by any technic which imitates the methods of attack and of slaughter used by the carnivora.

*In the course of evolution, injuries thus produced may well have been the predominating type of traumata to which our progenitors were subjected. In one particular respect there is an analogy between the response to trauma of some parts of the body of the individuals of a species susceptible to shock and the response to trauma of the individuals in certain other great divisions of the animal kingdom.

Natural selection has protected the crustaceans against their enemies by protective armor, e. g., the turtle and the armadillo; to the birds, it has given sharp eyes and wings, as, for instance, the wild goose to another species—the skunk—it has given a noisome odor for its protection. The turtle, protected by its armor against trauma, is in a very similar position to that of the sheltered brain of man and, like the brain, the turtle does not respond to trauma by an especially active self-protective nerve-muscular response, but merely withdraws its head and legs within the armored protection.

It is proverbially difficult to exhaust or to kill this animal by trauma.

The brain and other phylogenetically sheltered parts likewise give no exhausting self-protective nerve-muscular response to trauma. The skunk is quite effectively protected from violence by its peculiar odor.

This is indicated not only by the protective value of the odor itself, but also by the fact that the skunk has no efficient nerve-muscular mechanism for escape or defense; it can neither run fast nor can it climb a tree. Moreover, in encounters it shows no fear and backs rather than runs. The armadillo rolls itself into a ball for defense.

On these premises we should conclude that the turtle, the armadillo, and the skunk have fewer nociceptors than has a dog or man, and that they would show less response to trauma.

In two carefully conducted experiments on skunks and two on armadillos (an insufficient number) the energy discharged in response to severe and protracted trauma of the abdominal viscera was very much less than in similar experiments on dogs, opossums, pigs, sheep, and rabbits.

It was indeed relatively difficult to exhaust the skunks and armadillos by trauma. These experiments are too few to be conclusive, but they are of some value and furnish an excellent lead.

It seems more than a coincidence that proneness to fear, distribution of nociceptors, and susceptibility to shock go hand-in-hand in these comparative observations (Figs. 6, 7, and 8).

 

The discharge of energy caused by an adequate mechanical stimulation of the nociceptors is best explained in accordance with the law of phylogenetic association. That is, injuries awaken those reflex actions which by natural selection have been developed for the purpose of self-protection. Adequate stimulation

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