ADRENAL SECRETION IN STRONG EMOTIONS AND PAIN

If the secretion of adrenin is increased in strong emotional states and in pain, that constitutes a fact of considerable significance, for, as already mentioned, adrenin is capable of producing many of the bodily changes which are characteristically manifested in emotional and painful experiences. It is a matter of prime importance for further discussion to determine whether the adrenal glands are in fact roused to special activity in times of stress.

The Evidence that Adrenal Secretion Is Increased in Emotional Excitement

That blood from the adrenal veins causes the relaxation of intestinal muscle characteristic of adrenal extract or adrenin is shown in Fig. 3. The muscle was originally beating in blood which contained no demonstrable amount of adrenal secretion; this inactive blood was replaced by blood from the adrenal veins, obtained after quick etherization. Etherization, it will be recalled, is accompanied by a “stage of excitement.” Relaxation occurred almost immediately (at b). Then the rhythm was renewed in the former blood, and thereupon the muscle was surrounded with blood from the vein leading away from the left kidney, i. e., blood obtained from the same animal and under the same conditions as the adrenal blood, but from a neighboring vein. No relaxation occurred. By this and other similar tests the reliability of the method was proved.

In no instance did blood from the inferior vena cava of the quiet normal animal produce relaxation. On the other hand, blood from the animal after emotional excitement showed more or less promptly the typical relaxation. In Fig. 4 is represented the record of intestinal muscle which was beating regularly in Ringer’s solution. At a the Ringer’s solution was removed, and at b “excited” blood was added; after the preliminary shortening, which, as already stated, occurs at the first immersion in blood, the muscle lengthened gradually into complete inhibition. At c the “excited” blood was removed, and at d “quiet” blood was added in its place. The muscle at once began fairly regular rhythmic beats. At e the “quiet” blood was removed, and at f the “excited” blood was again applied. The muscle lengthened almost immediately into an inhibited state. In this instance the “excited” blood was taken after the cat had been barked at for about fifteen minutes.

The increase of effect with prolongation of the period of excitement is shown in Fig. 5. A is the record of contractions after the muscle was surrounded with “quiet” blood serum. B shows the gradual inhibition which occurred when the muscle was surrounded with defibrinated blood taken when the animal had been excited eleven minutes. And C is the record of rapid inhibition after fifteen minutes of excitement. In other instances the effect was manifested merely by a lowering of the tonus of the muscle, and a notable slowing of the beats, without, however, a total abolition of them.

The inference that this inhibition of contraction of the intestinal muscle is due to an increased amount of adrenal secretion in the “excited” blood de la Paz and I justified on several grounds:

(1) The inhibition was produced by “excited” blood from the inferior vena cava anterior to the mouths of the adrenal veins, when blood from the femoral vein, taken at the same time, had no inhibitory influence. Since blood from the femoral vein is typical of the cava blood below the entrance of the kidney veins, the conclusion is warranted that the difference of effect of the two samples of blood is not due to any agent below the kidneys. But that blood from the kidneys does not cause the relaxation is shown in Fig. 3. The only other structures which could alter the blood between the two points at which it was taken are the adrenal glands, and the material secreted by them would produce precisely the inhibition of contraction which was in fact produced.

(2) If in ether anesthesia the blood vessels leading to and from the adrenal glands are first carefully tied, and then the glands are removed, excitement four or five hours later, before the weakness that follows the removal has become prominent, does not alter the blood so that the typical inhibition occurs (see Fig. 6). Thus, although the animal shows all the characteristic signs of sympathetic stimulation, the blood, in the absence of the adrenals, remains unchanged.

(3) As already shown, sometimes the effect produced by the “excited” blood was prompt inhibition, sometimes the inhibition followed only after several beats, and sometimes a slowing and shortening of contractions, with a lower tone, were the sole signs of the action of adrenin. All these degrees of relaxation can be duplicated by adding to inactive blood varying amounts of adrenin. Fig. 7 shows the effects, on a somewhat insensitive muscle preparation, of adding adrenin, 1:1,000,000 (A), 1:2,000,000 (B), and 1:3,000,000 (C), to different samples of blood previously without inhibitory influence. These effects of adrenin and the effects produced by blood taken near the opening of the adrenal veins are strikingly analogous.

(4) Embden and v. Furth[1] have reported that 0.1 gram of suprarenin chloride disappears almost completely in two hours if added to 200 cubic centimeters of defibrinated beef blood, and the mixture constantly aerated at body temperature. “Excited” blood which produces inhibition loses that power on standing in the cold for twenty-four hours, or on being kept warm and agitated with bubbling oxygen. This change is illustrated in Fig. 8; the power of the “excited” blood to inhibit the contractions of the intestinal muscle when record A was written was destroyed after three hours of exposure to bubbling oxygen, as shown by record B. The destruction of adrenin and the disappearance of the effect which adrenin would produce are thus closely parallel.

All these considerations, taken with the proof that sympathetic impulses increase secretion of the adrenal glands, and taken also with the evidence that, during such emotional excitement as was employed in these experiments, signs of sympathetic discharges appeared throughout the animal from the dilated pupil of the eye to the standing hairs of the tail-tip, led us to the conclusions that the characteristic action of adrenin on intestinal muscle was in fact, in our experiments, due to secretion of the adrenal glands, and that that secretion is increased in great emotion.

The Evidence that Adrenal Secretion is Increased by “Painful” Stimulation

As mentioned in the first chapter, stimulation of sensory fibres in one of the larger nerve trunks is known to result in such nervous discharges along sympathetic paths as to produce marked inhibition of digestive processes. Other manifestations of sympathetic innervations—e. g., contraction of arterioles, dilation of pupils, erection of hairs—are also demonstrable. And since the adrenal glands are stimulated to activity by sympathetic impulses, it was possible that they would be affected as are other structures supplied with sympathetic fibres, and that they would secrete in greater abundance when sensory nerves were irritated.

The testing of this possibility was undertaken by Hoskins and myself in 1911. Since bodily changes from “painful” stimulation can in large degree be produced in an anesthetized animal, without, however, an experience of pain by the animal, it was possible to make the test quite simply. The sensory stimulus was a rapidly interrupted induced current applied to the sciatic nerve. The current was increased in strength as time passed, and thus the intensity of the effect, indicated by continuous dilation of the pupils, was maintained. There was no doubt that such stimulation would have caused very severe pain if the animal had not been anesthetized. Indeed, the stimulus used was probably much stronger than would be necessary to obtain a positive result in the absence of the anesthetic (urethane), which markedly lessens the irritability of visceral nerve fibres.[2] In different instances the stimulation lasted from three to six minutes. Throughout the period there was markedly increased rapidity and depth of breathing.

As Fig. 9 shows, the normal blood, removed from the vena cava before stimulation, caused no inhibition of the beating segment, whereas that removed afterwards produced a deep relaxation. Hoskins and I showed that the increased respiration which accompanies “painful” stimulation does not augment adrenal activity. We concluded, therefore, that when a sensory trunk is strongly excited the adrenal glands are reflexly stimulated, and that they pour into the blood stream an increased amount of adrenin.

Confirmation of Our Results by Other Observers

The foregoing experiments and conclusions were reported in 1911. In 1912, Elliott[3] brought confirmatory evidence by use of a method quite different from ours. As previously stated, he studied the effects of experimental procedures on adrenal secretion by a careful comparative quantitative assay of the adrenin content of the glands when one gland was isolated from the central nervous system and the other left connected. He took advantage of the action of morphia and of the substance Β-tetrahydronaphthylamine in evoking in cats all the appearances of great fright. After the animals had thus been “frightened,” he found that the adrenal gland which was still connected with the spinal cord was much depleted of its adrenin content compared with the other, isolated gland. And he observed, further, that animals newly brought to the laboratory, and evidently disturbed by the strangeness of their surroundings, had a considerably smaller amount of adrenin in their glands than other animals grown accustomed to the situation. Elliott also observed that prolonged excitation of a sensory nerve, such as the great sciatic, may cause the adrenin largely to disappear from the gland still connected with the central nervous system and subjected, therefore, to reflex influences.

Our conclusions have also been confirmed more recently (1913) by Hitchings, Sloan and Austin,[4] working in Crile’s laboratory in Cleveland. They used the same method which we had used to obtain blood and to test for adrenin, and found that after great fear and rage had been induced in a cat by the attempt of a muzzled dog to fight it, the adrenin reaction was clearly demonstrable. And just as we had noted that the reaction did not occur if the adrenal glands had been removed, they showed that it did not occur if the nervous connections with the spinal cord were previously severed.

The logic of all these experiments may be briefly summed up. That the adrenal glands are subject to splanchnic influence has been demonstrated anatomically and by the physiological effects of their secretion after artificial stimulation of the splanchnic nerves. Impulses are normally sent along these nerves, in the natural conditions of life, when animals become greatly excited, as in fear and rage and pain. There is every probability, therefore, that these glands are stimulated to extra secretion at such times. Both by an exceedingly delicate biological test (intestinal muscle) and by an examination of the glands themselves, clear evidence has been secured that in pain and deep emotion the glands do, in fact, pour out an excess of adrenin into the circulating blood.

Here, then, is a remarkable group of phenomena—a pair of glands stimulated to activity in times of strong excitement and by such nerve impulses as themselves produce at such times profound changes in the viscera; and a secretion given forth into the blood stream by these glands, which is capable of inducing by itself, or of augmenting, the nervous influences which induce the very changes in the viscera which accompany suffering and the major emotions. What may be the significance of these changes, occurring when conditions of pain and great excitement—experiences common to animals of most diverse types and probably known to their ancestors for ages past—lay hold of the bodily functions and determine the instinctive responses?

Certain remarkable effects of injecting adrenin into the blood have for many years been more or less well recognized. For example, when injected it causes liberation of sugar from the liver into the blood stream. It relaxes the smooth muscle of the bronchioles. Some old experiments indicated that it acts as an antidote for muscular fatigue. It alters the distribution of the blood in the body, driving it from the abdominal viscera into the heart, lungs, central nervous system and limbs. And there was some evidence that it renders more rapid the coagulation of the blood. There may be other activities of adrenin not yet discovered—it may coöperate with the products of other glands of internal secretion. And other glands of internal secretion may be stimulated by sympathetic impulses. But we were not concerned with these possibilities. We wished to know whether the adrenin poured out in pain and emotional excitement produced or helped to produce the same effects that follow the injection of adrenin. Our later researches were concerned with answers to this question.

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