The antinociceptive effect of iontophoretic direct application of diclofenac to arthritic knee-joints of rats |
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Authors: | Motta Andréa Fontoura Borges Junior Noé Gomes da Fonseca José Carlos Pio Tonussi Carlos Rogério |
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Affiliation: | 1. Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang 110001, PR China;2. Department of Immunology and Microbiology, Liaoning, Vocational College of Medicine, No. 2 Qiaosong Road, Shenyang 110101, PR China;3. Department of Sports Medicine and Joint Surgery/Orthopedic, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang 110001, PR China |
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Abstract: | This study compared the antinociceptive effect produced by cathodic iontophoresis of sodium diclofenac close to an arthritic knee-joint in rats with that of systemic application. Arthritic nocifensive incapacitation was induced by LPS (1 microg) injection into a knee-joint previously (72 h) primed with carrageenan (300 microg). Diclofenac (0.1, 0.25 and 0.5 mg/kg) given intraperitoneally 1 h after LPS injection caused dose-dependent inhibition of incapacitation. Diclofenac iontophoresis was performed by varying either the current density (0.1, 0.2, and 0.3 mA/cm2) or the duration of application (4, 10, 20 and 30 min) of a polyvinylpirrolydone-hydroxymethylcellulose gel containing 1% sodium diclofenac. A clear, current density-dependent effect was observed for 0.1, 0.2 and 0.3 mA/cm2 (10 min period), which was similar to the effect observed for the intraperitoneal application of 0.1, 0.25 and 0.5 mg/kg doses. Combining different application periods with different current densities, in a manner that resulted in the same total current (1.6 mA*min) application, did not produce similar therapeutic effects, but the antinociceptive effect was directly proportional to the current density. The ipsilateral iontophoresis (0.25 mA/cm2 x 10 min or 0.5 mA/cm2 x 4 min) of diclofenac produced an effect significantly greater than the same contralateral application (p<0.05). In conclusion, our results suggest that the therapeutic effect depends on the current density but not on the application time, and also that the iontophoretic, direct application to the inflamed knee-joint enhances the therapeutic effect probably as a result of the direct delivery of the drug. |
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