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Oral Tramadol may be Alternative to Paracetamol for Osteoarthritis

For patients with osteoarthritis (OA) of the knee, tramadol may be an alternative treatment to paracetamol, report researchers from Italy.

Although paracetamol is currently the first-line pharmacological therapy for osteoarthritis, its therapeutic benefit is limited by its lack of anti-inflammatory effects and its inability to adequately control pain in some patients. The efficacy in managing pain is increasingly being recognised with tramadol, although the pharmacological profile of this drug is not completely understood.

To evaluate the comparative benefits of paracetamol and tramadol in the treatment of OA, as well as to evaluate the mechanism of action of tramadol, M. Bianchi, MD, University of Milan, and colleague conducted a prospective, double-blind, study of 20 patients with OA (2 men and 18 women). Ten patients were randomised to tramadol (50 mg, 3 times daily) and 10 to paracetamol (500 mg, 3 times daily). Treatment was delivered for 7 days.

Primary outcomes evaluated were pain improvement (evaluated by a VAS scale) and changes in synovial fluid concentrations of interleukin-6 (IL-6) and substance P (SP). Plasma and synovial fluid concentrations of tramadol and its active metabolite (O-desmethyl-tramadol, M1) after oral administration were evaluated to assess the activity of tramadol.

Of the 18 evaluable patients (8 in the tramadol group and 10 in the paracetamol group), VAS scores taken prior to treatment (basal) and 2 hours after treatment showed that both treatments significantly reduced pain intensity (P < .05), with no significant differences between the two drugs.

For patients treated with tramadol, synovial fluid concentrations of SP were significantly reduced after 7 days of treatment (from basal of 106.6 to post-treatment of 56.5; P < .011). Similar significant reductions were not found in patients treated with paracetamol (basal of 99.6 to post-treatment of 66.5; P < .073). Changes of IL-6 synovial fluid concentrations were not significantly reduced with either drug, although patients receiving tramadol had a nonsignificant reduction of 189.2 basal to 118.1 post-treatment (P = .15), whereas patients on paracetamol showed no significant modifications after treatment with a change from 212.4 basal to 283.6 post-treatment (P = .31).

Evaluation of the activity of tramadol after oral administration showed considerable amount of tramadol in synovial fluid, with concentrations of M1 in both synovial fluid and plasma substantially lower than those of tramadol. The ratio of tramadol to M1 was 9.3 in synovial fluid and 14.7 in plasma.

The authors conclude that "tramadol offers a valid alternative to paracetamol for the treatment of patients with OA," and that the activity of tramadol may involve the modulation of inflammatory mediators and its ability, along with its active metabolite, to penetrate the synovial fluid.

International Immunopharmacology 2003;3:1901-1908. "Effects of tramadol on synovial fluid concentrations of substance P and interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol"

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