Neural circuit for psychological stress-induced hyperthermia

Psychological stress-induced hyperthermia (PSH) is a basic physiological stress response to increase physical performances to defend homeostasis and life from stressors, such as natural enemies. However, excessive and long-lasting stressors can lead to chronic hyperthermia, particularly recognized in humans as a psychosomatic symptom called “psychogenic fever.” The sympathetic and neuroendocrine responses that can contribute to PSH include brown adipose tissue (BAT) thermogenesis, cutaneous vasoconstriction, tachycardia and glucocorticoid secretion. Research on the central circuits underlying these stress responses has recently revealed several fundamental circuit mechanisms including hypothalamomedullary pathways driving the sympathetic stress responses. Psychological stress activates a monosynaptic glutamatergic excitatory neurotransmission from the dorsomedial hypothalamus (DMH) to sympathetic premotor neurons in the rostral medullary raphe region (rMR) to drive BAT thermogenesis and tachycardia, leading to the development of PSH. This glutamatergic neurotransmission could be potentiated by orexin neurons in the lateral hypothalamus through their projections to the rMR. Psychological stress also activates another monosynaptic pathway from the DMH to the paraventricular hypothalamic nucleus to stimulate the hypothalamo-pituitary-adrenal axis for the secretion of glucocorticoids. PSH is independent from the prostaglandin-mediated trigger mechanism for inflammation-induced fever, and several forebrain regions are considered to provide stress-driven inputs to the DMH to activate the sympathetic- and neuroendocrine-driving neurons. The circuit mechanism of PSH based on animal experiments would be relevant to understandings of the etiology of psychogenic fever in humans. This review describes the current understandings of the central circuit mechanism of PSH with recent important progress in research.