Franklin D. McMillan, DVM, DACVIM
Is Stress What We Think It Is?
Despite intensive research and analysis spanning a majority of the twentieth century, stress remains a confusing and controversial concept. Remarkable advances in the understanding of the physiological, psychological, and pathological correlates of the stress response have yet to lead to a unified, integrative framework for stress, and no consensus on a definition or methods for measurement has been reached.1 Stress is currently a widely and very loosely used term for describing complex and incompletely understood somatic, emotional, and cognitive responses to novel, challenging, and threatening stimuli, as well as many other energy-demanding events.2 Unfortunately, stress has now come to serve as an over-simplified catch-all term used to refer to virtually any aversive physical or psychological condition.3
Stress and emotion are deeply intertwined concepts. Each is mutually dependent on the other; they coexist in many, and possibly all, situations in which stress mechanisms are activated.4 The ambiguity over the relationship between stress and emotion is reflected in the terminology used, which routinely blends and frequently equates the two concepts. In the scientific literature, "stress" and "unpleasant emotion" (e.g., fear, anxiety, etc.) are often treated as one and the same and are regularly used interchangeably. For example, two recent treatises on the association of stress and emotion4,5 use the terms as virtual equivalents throughout the texts, making no meaningful effort to differentiate the two.
To frame the problem inherent in the relationship between stress and emotion, we look at two key goals in animal care: 1) minimize unpleasant emotions and 2) minimize stress. Are the two goals, and the methods of achieving them, the same? If not, how do they differ? Do aversive events, such as separation from a bonded social companion, elicit stress, emotion, or both? Or do aversive events elicit an emotion, which elicits stress, or stress, which elicits emotion? When a dog with severe separation anxiety is left at home and destroys furniture and frantically claws the door to escape, is the dog experiencing stress, anxiety, fear, or something altogether different? Or is the dog experiencing distress, and is that different from stress or emotion? This confusion permeates the scientific literature.
Despite the lack of consensus on the definition of stress, most researchers agree that central to the concept of stress is the preservation of homeostasis. Homeostasis refers to a dynamic state of psychological and physiologic equilibrium or balance in which vital physiological parameters such as body temperature, acidity, blood glucose level, and so on, are all maintained in a range, often narrow, that is optimally supportive of well-being and survival.4,6-8 A commonly used definition of stress is "the response to the body of any actual or threatened disturbance of homeostasis."9
Deviations from homeostasis represent a threat to and reduced chances for fitness; hence, animals have evolved effective mechanisms for detecting and correcting such deviations.10 Emotional responses, like somatic responses, function to preserve, protect, or otherwise maintain homeostasis. Examples of the specificity of emotions include fear when approaching a cliff edge, loneliness (or other feelings of isolation and separation) when social animals are separated from companions, and frustration when unable to achieve a desired goal.11
In all, a fundamental development of evolved defense mechanisms is the ability to recognize and respond in a non-random, goal-oriented, and specific fashion to threats to the individual's homeostasis. On encountering a stimulus that is perceived by the animal as endangering homeostasis, the animal activates a highly specific homeostasis-preserving response.
The Stress Response
The process referred to as "the stress response" is traditionally viewed as comprising a set of neuroendocrine responses to aversive stimuli. Stress research has focused largely on the autonomic, or sympathoadrenal (SA), and HPA systems. The SA response involves the sympathetic nervous system (SNS), adrenal medulla, and catecholamine release. The HPA response involves the hypothalamus, anterior pituitary gland, adrenal cortex, and glucocorticoid release.3 In addition to these two major neuroendocrine components of the stress response--which are present to some degree in most, but not all, stress responses--numerous other hormones are secreted (e.g., prolactin, vasopressin, endorphins, enkephalins, vasoactive intestinal peptide, substance P, serotonin, glucagon, and renin).12-14 It is now well accepted that there is no single invariant metabolic stress response and that "the stress response" actually refers to a relatively diverse array of different patterns of physiologic changes observed when organisms encounter different types of aversive or threatening stimuli.12-14
On presentation of a sufficiently threatening aversive stimulus, the sympathoadrenal response is activated.15 The SNS exerts efferent neural control over a number of diverse mechanisms that contribute to homeostasis restoration.3 The SNS is the primary component of the fight-or-flight response (which, to be accurate, should be termed the fight-or-flight-or-freeze response) in emergency situations.3,14 The secretion of the catecholamines epinephrine and norepinephrine causes numerous changes supportive of the need for emergency action. Physiologic changes include increased heart rate and contractility, vasoconstriction in nonvital organs, and enhanced gluconeogenic activity of glucocorticoids.16 Cognitive mental changes include heightened arousal and vigilance.17 The HPA response is activated concurrently with the SNS response, but its effects manifest more slowly.3 The aversive stimuli shown to initiate HPA responses include a wide array of physical (e.g., heat, cold, electric shock, sleep deprivation, disease, and injury) and psychological (e.g., uncertainty, unpredictability, anxiety, fear, conflict, social conflict, and lack of control) factors.3,18 Of the two, psychological factors have been demonstrated to be the most potent stimuli for HPA activation.3
The Health Effects of Stress
Clinicians in human medicine have long observed that "stress" contributes to the course of disease states and that social and environmental factors can influence susceptibility to illness and disease by altering the responsiveness of the immune system.19 Today, an extensive body of literature reveals the influence of emotional states on the course and outcome of physical illnesses in human and non-human animals.
The biological basis and evidence for an intersystemic communicative network has recently been uncovered in neuropeptide research. Neuropeptides, short chains of amino acids originally known for their role as neurotransmitters, function as hormone-like messenger molecules, transmitting information from the secreting cell to other cells by binding to and activating specific receptors on cell surfaces.20 In the CNS of mammals, neuropeptides and their receptors are most densely concentrated in the limbic regions, classically known to contain the brain's emotional circuitry.20,21 Neuropeptides and their receptors originally were believed to be confined to and thus act solely within the nervous system. It has recently been found that endorphins are produced not only by cells of the CNS but also by cells of the immune system. Theirs and other's findings established that the immune system was communicating not only with the endocrine system but also with the nervous system and the brain, using a chemical mechanism that consisted of opiate neuropeptides and their receptors to code for information.21,22 With the additional finding that the CNS contains receptors for immunopeptides such as interleukins, cytokines, and lymphokines21 and that interleukins may modulate the actions of opioid peptides in animals,23 it became clear that the immune and nervous systems were communicating bidirectionally24,25; the immune system was capable of sending information to the brain via immunopeptides and receiving information from the brain via neuropeptides.21
At the same time, results of studies continued to elucidate the long-recognized integration of the endocrine and nervous system revealing, for example, that stress-induced immunomodulation in animals is mediated through glucocorticoid hormones and endogenous opioids, among other biochemical processes.26 The influence of the hypothalamic-pituitary-adrenal axis on immunologic function was determined to be one of the most important mechanisms of intersystemic communication.
The harm of stress comes from the stressful experience and the stress response itself. Although the literature is vast and spans nearly 100 years on the effects of the stress response--the long-term effects of a prolonged activation of the stress response leading to adverse health effects--very little attention has been paid to the short-term effects--the conscious affective experience. It is, however, the short-term harm of stressful experiences that animal caregivers are working the hardest to minimize.
The protective function of the stress response--energy mobilization, suppression of noncritical bodily functions, mental arousal and vigilance--is adaptive in the short run but not suited for and very costly in the long run. In an animal's natural environment, threats rarely persist for more than a few minutes, which would appear to be the most likely reason that stress mechanisms have evolved to be beneficial only for the short term. When the stress response remains activated for prolonged periods--in situations rarely occurring in the natural environment, such as confinement, deficient stimulation, and chronic or extreme overcrowding--the harm becomes manifest in the form of somatic and mental pathology.
In the face of chronic stress, virtually no aspect of the animal organism escapes harm, including a wide array of disorders of the immunologic, hemolymphatic, gastrointestinal, cardiovascular, musculoskeletal, nervous, urinary, and reproductive systems.2,27,28
A very small sampling of stress-induced health effects documented in animals:
Anxiety and other emotional and psychosocial stressors in experimental animals result in low immunocompetence to cancer, infective agents, and other disease processes that the body resists with cell-mediated immunity.29 Viral and neoplastic diseases are enhanced in animals subjected to emotional stress; the mechanism of enhancement is at least partially through compromised immunologic competence of the host. Emotions and anxiety in animals can have lethal consequences.29 Emotional stimuli profoundly affect cellular and humoral defenses in animals.19 Emotional stress in the form of fear of punishment will alter activity of the immune system of the rat.19 Mice maximally protected from chronic anxiety and other environmental stressors had significantly less incidence of mammary tumor.30 The onset of clinical signs of idiopathic lower urinary tract disease in cats is associated with aversive environmental stimuli.31
Emotions associated with social affiliation and bonding, regulated largely, if not solely, by endogenous opioids,32 caused a wide variety of pathologic effects if social bonds are disrupted, severed, or impaired. Completely weaned squirrel monkeys that were separated from their mothers had immune suppression at 7 and 14 days after separation.33 Those monkeys that were placed in cages with others had less immunosuppression than those caged alone.33 A 2-year study of male cynomolgus monkeys showed that monkeys in groups where social bonds were continually disrupted by the researchers had reduced immune function, compared with those in the "stable" group.34 Disruption of social relationships caused a significant decrease in survival among Rhesus monkeys inoculated with simian immunodeficiency virus, as compared to simian immunodeficiency virus-positive control monkeys not separated from familiar social companions.35 Separation anxiety in dogs, resulting from separation of dogs from the human companions to which they have formed social bonds, can cause intestinal disorders such as diarrhea and bloody stools.36
Sources of Stress for the Hospitalized Veterinary Patient
It has been noted that in human medicine, most hospitals today are designed to meet the needs of technology more than the emotional and psychological needs of the patient.37 For example, while there is extensive research on the benefits of social support and that contact with caring individuals during stressful situations is beneficial to health, hospitals typically separate patients and their families.37
Stressors inherent in the veterinary hospital environment include threatening smells, sounds (including those of frequencies inaudible to humans), lights (too bright and/or too many hours per day), activity and commotion, insufficiently stimulating environment, rough handling, unfamiliar people and other animals, pain, feelings of illness, inability to empty bladder or bowels, and unappealing food. These stressors will elicit different unpleasant feeling states on an acute basis and adverse health effects (see above) on a chronic basis.
Identifying Stress in the Hospitalized Veterinary Patient
The first rule of recognizing stress in animals the object is not to look for signs of "stress." We are looking for signs of specific unpleasant emotions that a stressor elicits, such as fear, anxiety, depression, helplessness, isolation/loneliness, separation anxiety, anger, and frustration. No uniform description of what "stress" looks like in any animal will encompass the array of emotional states that the animal experiences as stress, and without this precision the management of stress (see below) can not achieve the greatest effectiveness. Examples of signs in dogs include: for fear--restlessness, escape attempts, hiding, lack of appetite, and listlessness; for frustration--play bouncing, pacing, wall bouncing, and bedding chewing; and for social isolation--inactivity as well as increased movement, excessive vocalization, circling.38,39
The first and most important aspect of stress management is to discard the conventional and near universal view of stress--a pressure or tension that an individual experiences when challenged in some way--is wrong. To achieve effective management of stressful events, we must identify and target the underlying active emotional component(s). Declaring that the dog in the kennel is "stressed" provides virtually no useful information for providing control of the harmful experience, as the 'stress' could be due to fear, anxiety, separation distress, isolation/loneliness, boredom, frustration, helplessness, pain, hunger, constipation, or other unpleasant emotional or physical states. In selecting appropriate methods for alleviating stress it is necessary to address the specific emotional state that is harming the animal, not some vague, catch-all concept called 'stress.'
Identifying the eliciting stimulus of the negative emotion is the second factor in stress management. The potential stressors for veterinary patients are listed above. These sources must be eliminated or minimized. The single greatest benefit in this regard is to minimize hospitalization and encourage home care of the patient.
Because we are not always able to eliminate stressors, we often must rely on other methods to alleviate the impact on the animal. Human contact and companionship has a beneficial effect in alleviating anxiety, fear, and even pain in some animals. Promoting owner visitation, even to the point of in-hospital sleep-overs with their pets, can provide valuable support for the healing animal. Music can also be of benefit; studies have demonstrated an antianxiety effect of classical music in dogs. Aromatherapy--lavender essence, chamomile, and DAP in dogs and Feliway in cats--has also shown important antianxiety effects. Pharmacotherapy has proven benefits for anxiety, fears/phobias, separation anxiety, depression, and learned helplessness.
Overall, given the vital role of the stress response in animal defense systems, the ideal goal of stress management programs would be to lessen the intensity and mental impact of the unpleasant event and protect against pathologic somatic and mental effects while ensuring that the body's ability to respond to a new challenge or threat remains adequate to mount an effective defensive response.18 This optimizes healing in animals recovering from illness or surgery.
1. Burchfield SR. Psychosom Med 1979;41:661.,
2. Riley V. Science 1981;212:1100.,
3. Clark JD, et al. Lab Anim Sci 1997;47:571.,
4. Lazarus RS. Stress and emotion 1999;New York:Springer.,
5. LeDoux J. The emotional brain 1996;New York:Simon & Schuster.
6. Sapolsky RM. In: Kahneman D, et al. (eds), Well-being. 1999;New York:Russell Sage Foundation:453.,
7. McEwen BS. Brain Res 2000;886:172.,
8. Charmandari E, et al. Horm Res 2003;59:161.,
9. Day TA. Prog Neuro-Pharmacol Biolog Psychiat 2005;29:1195.,
10. Panksepp J. Affective neuroscience 1998;New York:Oxford University Press.,
11. Rolls ET. Behav Brain Sci 2000;23:177.,
12. Mason JW. In: Levi L (ed), Emotions 1975;New York, Raven Press:143.,
13. Mason JW, et al. In: Serban G (ed), Psychopathology of human adaptation 1976;New York,Plenum Press:147.,
14. Moberg GP. J Am Vet Med Assoc 1987;191:1207.,
15. Dunn AJ, et al. Brain Res Rev 1990;15:71.,
16. Bond RF, et al. Fed Proc 1985;44:281.,
17. Sapolsky RM. Why zebras don't get ulcers 1994;New York:W.H. Freeman.,
18. Miller DB, et al. Metabolis 2002;51 Suppl 1:5.,
19. Bohus, et al. In: Ader R, et al. (eds), Psychoneuroimmunology (2nd Ed) 1991;New York:Academic Press:807.,
20. Pert CB, et al. J Immunology 1985;135:820.,
21. Pert CB. Molecules of emotion 1997;New York:Scribner.,
22. Blalock JE, et al. Biochem Biophys Res Commun 1981;101:472.,
23. Puppo F, et al. In: Negri M, et al. (eds). Clinical perspectives in endogenous opioid peptides 1992;Chichester:John Wiley & Sons:47.,
24. Solomon GS, et al. In: Plotnikoff NP, et al. (eds). Enkephalins and endorphins 1986;New York:Plenum Press:129.,
25. Blalock JE, et al. J Immunology 1985;135:858.,
26. Shavit Y. In: Ader R, et al. (eds), Psychoneuroimmunology (2nd Ed) 1991;New York:Academic Press:789.,
27. McEwen BS. Metabolis 2002;51 Suppl 1:2.,
28. Schulkin J. Horm Behav 2003;43:21.,
29. Riley V. Science 1981;212:1100.,
30. Riley, et al. In: Ader R (ed), Psychoneuroimmunology 1981;New York:31.,
31. Buffington CAT, et al. Vet Clin No Amer: Sm Anim Pract 1996;26:317.,
32. Panksepp J, et al. Neurosci Biobehav Rev 1980;4:473.,
33. Kiecolt-Glaser JK, et al. In: Ader R, et al. (eds), Psychoneuroimmunology (2nd Ed) 1991;New York:Academic Press:849.,
34. Serpell J. In the company of animals 1996;Cambridge:Cambridge University Press.,
35. Capitanio JP, et al. Psychosom Med 1998;60:235.,
36. Voith VL, et al. Compend Contin Educ Pract Vet 1985;7:42.,
37. Schweitzer M, et al. J Altern Compliment Med 2004;10 Suppl 1:S71.,
38. Stephen JM et al. J Appl Anim Welf Sci 2005;8:79.,
39. Beerda B, et al. Anim Welf 2000;9:49.