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Medical Hypotheses 2011-Nov

Are prostatitis symptoms associated with an isoprostane-mediated vicious circle?

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Prostatitis is a disease that seriously affects the quality of patients' life. In the majority of cases, chronic prostatitis (chronic pelvic pain syndrome--CPPS) has an unclear pathogenesis. Anti-inflammatory and anti-infectious treatments have remained controversial. According to the latest research, prostatitis has been associated with oxidative stress (OxS) and/or OxS-related genetic polymorphisms. We have observed that prostatitis patients have systemic OxS in case of inflammation and pain. We propose a new explanation for the role of OxS in the pathogenesis of prostatitis and describe the putative OxS-related pathways in detail. The neural vicious circle starts by activation of primary sensory afferents. Glutamate mediates the signal to the neurons in the dorsal horn of the spinal cord, and facilitates calcium influx into their mitochondria. The latter causes an increased production of superoxide radicals. If the superoxide production is not effectively controlled by mitochondrial superoxide dismutase (Mn-SOD), then superoxide leads to OxS and lipid peroxidation. Consequent release of electrophilic lipid peroxidation products (LPP) from dorsal horn of the spinal cord causes pain by activating the primary sensory afferents, again. Additional LPP-mediated causes of pain include glutathione depletion and neuron sensitisation by isoprostanes. Excretion of LPP into urine may exert positive feedback as well. Currently, different information exists about chronic prostatitis (inflammation, pain, oxidative stress, neural sensitisation, lower urinary tract symptoms). The clear links between these data are actually absent. We propose that vicious circle based on LPP, especially isoprostanes, is the linking mechanism.

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