It should occasion no surprise that there are in the brain no receptors, the mechanical stimulation of which can cause pain, because its bony covering has always prevented the adaptive implantation within it of contact pain receptors. Dr. Frazier tells me that in the course of his operations on the brains of unanesthetized patients he is able to explore the entire brain freely and without pain. From my own experience I am able to confirm Dr. Frazier's observation. In addition, the two-stage operation for the excision of the Gasserian ganglion provides an observation of extraordinary interest. If at the first seance the ganglion is exposed, but is not disturbed except by the iodoform gauze packing, then on the following day the gauze may be removed, the ganglion picked up, and its branches and root excised without anesthesia and without pain. The same statement and explanation may be made regarding the distribution of pain receptors for physical contact within the parenchyma of the liver, the gall-bladder, the abdominal viscera, the spleen, the heart, the lungs, the retroperitoneal tissue, the deep tissue of the back, the vertebrae, and in certain portions of the spinal cord. Just what is the distribution of the receptors for heat and for cold I am unable to state, but this much we do know, that without anesthesia the intestines may be cauterized freely without the least pain resulting, and in animals the cauterization of the brain causes no demonstrable change in the circulatory or respiratory reactions. It is probable therefore that the distribution of the pain receptors for physical contact and for heat are limited to those parts of the body that have been exposed to injurious contacts with environment. Of special significance is the pain which is due to cold, which increases muscular tone and produces shivering. The general increase in muscular tone produces an interesting postural phenomenon: the limbs are flexed and the body bent forward, a position which probably is due to the fact that the flexors are stronger than the extensors. As muscular action is always accompanied by heat production, the purpose of the muscular contraction and the shivering is quite certainly caused by cold to assist in the maintenance of the normal body temperature. We have now discussed many of the causes of pain and in each instance we have found an associated muscular action which apparently serves some adaptive purpose (Figs. 24 and 25). If we assume that pain exists for the purpose of stimulating muscular reactions, we may well inquire what part of the nervous are is the site of the sensation of pain--the nerve-endings, the trunk, or the brain? Does pain result from physical contact with the nerve-endings, with the physical act of transmitting an impression along the nerve trunk, or with the process within the brain-cells by which energy is released to cause a motor act?