Surgery, burns, and migraine headaches in people can evoke vasopressin release from nerve endings in the posterior pituitary. Circulating vasopressin can influence vascular tone and diuresis and might also modulate nociception (Berson et al., 1983). Surgical trauma leads to increases in circulating neuropeptides, such as substance P and calcitonin gene-related peptide, possibly from unmyelinated nerve fibers activated at the site of inflammation and injury. Those neuropeptides are important in plasma extravasation and in the release of histamine from mast cells and serotonin from platelets. Their physiologic role after circulation in plasma is unknown.
Responses to persistent stressors, such as chronic stress or distress, are more variable than responses to acute stress; catecholamines might return to normal values, and corticosteroid concentrations might be increased, unchanged, or decreased. Thus, changes in concentrations of pituitary and adrenal hormones can be used as markers of acute stress, but their usefulness in the recognition of chronic stress or distress is questionable at best.
Biochemical markers are not unequivocal indicators of either pain or distress, but, when used in conjunction with behavioral and environmental data, they can reinforce a diagnosis. An acute stressor can produce a transient but important change in some characteristics; a chronic stressor can lead to the establishment of a new steady state of plasma hormones and heart function that might not be very different from the original. Different animals can respond to a given event differently, sometimes because of a lack of opportunity to habituate or acclimate. Care should be exercised when the effects of stress or distress could interfere with experimental results, because laboratory facilities and husbandry procedures can have different effects on individual animals.
It is not always possible to use behavioral or physiologic measures to distinguish between pain-induced distress and distress induced by other stimuli, but the use of pharmacologic techniques offers some interesting options in this regard. If an animal's behavior returns to normal after the administration of an analgesic, but not after administration of an anxiolytic, one would be justified in concluding that the distress was caused by a painful stimulus. One could similarly find that the distress was induced by fear or anxiety, rather than pain.
Other drug-based approaches that raise some intriguing questions about animal distress include the recent investigations of the effects of opioid receptor antagonists on stereotypic behaviors in animals. Stereotypic behavior in a confined animal is sometimes considered to be a sign of distress. It is interesting that antagonists reduce or eliminate bar-chewing in confined pigs, crib-biting in stabled horses, and lick granulomas in dogs (Cronin et al., 1986; Dodman et al., 1987; White, 1990).