The antinociceptive effect of iontophoretic direct application of diclofenac to arthritic knee-joints of rats.
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.
Motta
Andréa Fontoura
AF
Departamento de Prevenção, Avaliação e Reabilitação Física, State University of Santa Catarina (UDESC), Brazil.
Borges Junior
Noé Gomes
NG
da Fonseca
José Carlos Pio
JC
Tonussi
Carlos Rogério
CR
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000276:immunology; D006614:Hindlimb; D007270:Injections, Intra-Articular; D007274:Injections, Intraperitoneal; D007478:Iontophoresis / Q000379:methods; D007596:Joints; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D004008:Diclofenac