A possible neural basis for stress-induced hyperalgesia

Intense stress and fear have long been known to give rise to a suppression of pain termed stress-induced analgesia, mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of stress-induced hyperalgesia, the neurobiological basis for this effect remains almost entirely unknown. Using simultaneous single-cell recording and functional analysis, we show here that stimulation of the dorsomedial nucleus of the hypothalamus, known to be a critical component of central mechanisms mediating neuroendocrine, cardiovascular and thermogenic responses to mild or emotional stressors such as air puff, also triggers thermal hyperalgesia by recruiting pain-facilitating neurons ON-cells, in the rostral ventromedial medulla. Activity of identified RVM ON-cells OFF-cells and NEUTRAL cells. nocieptive withdrawal thresholds rectal temperature , and heart rate were recorded in lightly anethetized rats. In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.