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OBJECTIVE: To determine whether ibuprofen-arginine has a cyclooxygenase-independent pain modulating property in addition to its known antiinflammatory effect. METHODS: Patients with chronic low back pain were randomly divided into 2 groups treated either with oral ibuprofen-arginine (400 mg) or with placebo. Blood was drawn from study subjects before, during, and after treatment and they were asked each time about the intensity of their pain. Concentrations of nitric oxide (NO) metabolites were determined. RESULTS: Twenty minutes after intake of ibuprofen-arginine, but not after placebo, there was a relevant and significant reduction of NO metabolites in serum. In both groups there was significant analgesic effect compared to baseline. CONCLUSION: An early lowering of the serum NO metabolite levels after ibuprofen-arginine administration could be detected in patients with chronic low back pain.