Definitions of stress and sympathetic neuronal responses.

1. The precise physical definitions of stress as a force per unit area and of strain as the deformation of a solid subjected to that force are conceptually similar to the demands placed upon living organisms and the responses of organisms to those demands. 2. Cannon recognized that a "breaking strain" at a "critical stress" level can overwhelm homeostatic mechanisms and suggested that such a state is signaled by appearance of "secondary, irrelevant effects." The primary mechanisms of maintaining homeostasis are highly specific; and compensatory responses are mediated by the autonomic nervous system, and the less specific responses are mediated by the adrenal medullary hormone, epinephrine. 3. Selye extended this concept to include other hormonal responses, particularly of the hypothalamic-pituitary-adrenal axis, as components of a stereotypic response common to all stresses. He redefined stress as a state in which this stereospecific response has been evoked and popularized the notion that a variety of diseases are produced as a result of excessive or deficient adaptive processes during the stress response. 4. Both Cannon and Selye recognized that the responses to stresses differ among individuals and that such differences are due to genetic differences as modified by experience (Selye called these "conditioning factors"). Both attributed highly specific homeostatic responses to nervous control and both recognized that hormonal responses are necessarily less specific than neuronal responses. 5. Selye's concept of a single stereotypic syndrome that results from any demand upon the body, however, needs to be modified to reflect differences in the pattern of responses to various stresses. Data on responses to several stresses show that when homeostatic mechanisms do not predominate, the pattern of nonspecific, particularly hormonal, responses may differ among stresses. The essential fact, however, that most demands upon the body, when exceeding a critical level, elicit an array of complex neuroendocrine responses, and that these responses may have harmful effects, remains a landmark contribution.