Repeated sound stress enhances inflammatory pain in the rat

While it is well established that acute stress can produce antinociception, a phenomenon referred to as stress-induced analgesia, repeated exposure to stress can have the opposite effect. Since, chronic pain syndromes, such as fibromyalgia and rheumatoid arthritis, may be triggered and/or exacerbated by chronic stress, we have evaluated the effect of repeated stress on mechanical nociceptive threshold and inflammatory hyperalgesia. Using the Randall-Selitto paw pressure test to quantify nociceptive threshold in the rat, we found that repeated non-habituating sound stress enhanced the mechanical hyperalgesia induced by the potent inflammatory mediator, bradykinin, which, in normal rats, produces hyperalgesia indirectly by stimulating the release of prostaglandin E-2 from sympathetic nerve terminals. Hyperalgesia induced by the direct-acting inflammatory mediator, prostaglandin E-2 as well as the baseline nociceptive threshold, were not affected. Adrenal medullectomy or denervation, reversed the effect of sound stress. In sound stressed animals, bradykinin-hyperalgesia had a more rapid latency to onset and was no longer inhibited by sympathectomy, compatible with a direct effect of bradykinin on primary afferent nociceptors. In addition, implants of epinephrine restored bradykinin-hyperalgesia in sympathectomized non-stressed rats, lending further support to the suggestion that increased plasma levels of epinephrine can sensitize primary afferents to bradykinin. These results suggest that stress-induced enhancement of inflammatory hyperalgesia is associated with a change in mechanism by which bradykinin induces hyperalgesia, from being sympathetically mediated to being sympathetically independent. This sympathetic-independent enhancement of mechanical hyperalgesia is mediated by the stress-induced release of epinephrine from the adrenal medulla. (C) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.