Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite.

Three types of overlap occur among the disease states chronic fatigue syndrome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and posttraumatic stress disorder (PTSD). They share common symptoms. Many patients meet the criteria for diagnosis for two or more of these disorders and each disorder appears to be often induced by a relatively short-term stress which is followed by a chronic pathology, suggesting that the stress may act by inducing a self-perpetuating vicious cycle. Such a vicious cycle mechanism has been proposed to explain the etiology of CFS and MCS, based on elevated levels of nitric oxide and its potent oxidant product, peroxynitrite. Six positive feedback loops were proposed to act such that when peroxynitrite levels are elevated, they may remain elevated. The biochemistry involved is not highly tissue-specific, so that variation in symptoms may be explained by a variation in nitric oxide/peroxynitrite tissue distribution. The evidence for the same biochemical mechanism in the etiology of PTSD and FM is discussed here, and while less extensive than in the case of CFS and MCS, it is nevertheless suggestive. Evidence supporting the role of elevated nitric oxide/peroxynitrite in these four disease states is summarized, including induction of nitric oxide by common apparent inducers of these disease states, markers of elevated nitric oxide/peroxynitrite in patients and evidence for an inductive role of elevated nitric oxide in animal models. This theory appears to be the first to provide a mechanistic explanation for the multiple overlaps of these disease states and it also explains the origin of many of their common symptoms and similarity to both Gulf War syndrome and chronic sequelae of carbon monoxide toxicity. This theory suggests multiple studies that should be performed to further test this proposed mechanism. If this mechanism proves central to the etiology of these four conditions, it may also be involved in other conditions of currently obscure etiology and criteria are suggested for identifying such conditions.