Linking work factors to neck myalgia: the nitric oxide/oxygen ratio hypothesis

The pathophysiological link between work-related exposures and neck myalgia remains a puzzle. According to the hypothesis presented here, neck myalgia is evoked when low-level contractions in the trapezius muscle are combined with sympathetic vasoconstriction due to psychological stress or prolonged head-down neck flexion at work. These ischemic contractions increase nitric oxide/oxygen concentration ratio in the muscle fibres, enhancing herewith the reversible inhibition of mitochondrial cytochrome oxidase by nitric oxide. The result is depletion of adenosine triphosphate, which elicits production/efflux of lactic acid, in turn activating and sensitising proton-sensitive nociceptive fibres in the connective tissue, causing myalgic pain and tenderness. High estrogen-level, which gives a high expression of nitric oxide synthase in the muscle, accentuates the situation. During episodes of sustained inhibition of cytochrome oxidase by nitric oxide, peroxynitrite may be produced and cause irreversible inactivation of several enzymes in the mitochondrial electron-carrier chain. With repeated episodes, an increasing part of the enzymatic capacity for cellular respiration is inactivated. Even if this process only takes place within a small portion of the muscle fibres, it may contribute to frequent exacerbations of pain. Effects of peroxinitrite may also explain the mitochondrial abnormalities found in the trapezius muscle of many neck myalgia patients. Adrenergic antagonists and nitric oxide synthase inhibitors could reduce symptoms. Ascorbic acid, alpha tocopherol, and flavonoids, which are safe and effective scavengers of peroxynitrite, could prevent chronicity. The most effective non-pharmacological measure may be to reduce exposure to prolonged head-down neck flexions and psychosocial stress at work.