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 syndr ome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and postt raumatic 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 whi ch is followed by a chronic pathology, suggesting that the stress may act b y inducing a self-perpetuating vicious cycle. Such a vicious cycle mechanis m has been proposed to explain the etiology of CFS and MCS, based on elevat ed levels of nitric oxide and its potent oxidant product, peroxynitrite. Si x positive feedback loops were proposed to act such that when peroxynitrite levels are elevated, they may remain elevated. The biochemistry involved i s not highly tissue-specific, so that variation in symptoms may be explaine d by a variation in nitric oxide/peroxynitrite tissue distribution. The evi dence 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, i t is nevertheless suggestive. Evidence supporting the role of elevated nitr ic oxide/peroxynitrite in these four disease states is summarized, includin g induction of nitric oxide by common apparent inducers of these disease st ates, markers of elevated nitric oxide/peroxynitrite in patients and eviden ce for an inductive role of elevated nitric oxide in animal models. This th eory appears to be the first to provide a mechanistic explanation for the m ultiple 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 multipl e 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. (C) 2001 Harcou rt Publishers Ltd.