Chronic stress and pain - a plea for a concerted research program.

Chronic functional pain syndromes have commonly been associated with ongoing exposure to stress or with post-traumatic stress disorder (PTSD). Considering the inherent tremendous burden for the affected patients, their families and for society, it is critical that we better understand the cause and effect relationships between chronic stress and pain. In this context, one recently advocated approach would be to target altered hormonal pathways [1]. The literature is now replete with studies indicating that pain syndromes such as fibromyalgia [5], chronic pelvic pain [6], certain types of low-back pain [4] and rheumatic arthritis [10] may be associated with a dysfunctional reactivity of the hypothalamic–pituitary–adrenal (HPA) axis. The blunted adrenocortical reactivity (relative hypocortisolism) observed in these studies may be related to chronic exposure to stress or to PTSD (for review see [9]). One hypothesis is that this may lead to a disinhibition of the secretion of proinflammatory mediators by immunocompetent and glial cells, resulting in an ongoing sensitization of nociceptive neurons and hence in an enhanced pain sensitivity [3]. Taken together, these findings seem to point towards the adequacy of a psychoneuroimmunological approach focusing on the contribution of stress-related dysfunctional communication among the nervous, immune and endocrine systems in pathophysiological nociceptive processing. A cautious approach, however, is essential. We should not fall to the temptation to assume that all hypotheses made and data collected are generalizable. In this context, Kraus and colleagues [7] have published a very interesting study in the present issue of Pain. The investigators used psychophysical methods to characterize pain sensitivity in PTSD, a disease commonly associated with chronic pain, current pain and pain-related disability. The main and somewhat intriguing finding was a reduced pain sensitivity (significantly increased heat and cold pain thresholds) in both combat veterans suffering from PTSD and combat controls as compared to healthy controls. With longer lasting heat stimuli, the authors could also discriminate between veterans with and veterans without PTSD, the former having significantly lower pain reports. This paper is very important since the authors are among the first to provide evidence that stress-related diseases may under certain conditions be associated with a depressed pain sensitivity rather than with an enhanced pain sensitivity. These data raise several key issues, but some of these have been only partly addressed by the investigators. In the following I discuss some points that may deserve particular attention and that may constitute useful guidelines for future research on interactions between stress and pain: