title: Comparison between oral and intra-articular antinociceptive effect of dexketoprofen and tramadol combination in monosodium iodoacetate-induced osteoarthritis in rats.
abstract: Dexketoprofen and tramadol, alone or in combination, were evaluated after oral or intra-articular administration on knee osteoarthritis nociception induced by intra-articular (i.ar.) monosodium iodoacetate (MIA, 1 mg/25 µl) in the rat right knee while the left knee received saline (25 µl). Seven days after MIA treatment, dexketoprofen, tramadol, their combination or the vehicle were administered. Nociception was evaluated as alteration in hind limb weight distribution with Incapacitance tester at different time-points after drug administration. Oral dexketoprofen (0.1-1 mg/kg) or tramadol (0.5-5 mg/kg) induced maximal antinociception at 1 and 5 mg/kg, respectively. Their combination dose-dependently increased the intensity and duration of antinociception, that was additive and lasted up to 3 days. Also the intra-articular administration of dexketoprofen or tramadol (10-100 µg/25 µl) inhibited MIA-induced nociception, and the combination of the lower doses (10 µg/25 µl) produced a long lasting more than additive antinociceptive effect indicating a synergistic interaction between the two drugs. This effect was significantly reduced by naloxone (10 μg/25 μl, i.ar.) co-administered with both compounds. The intra-articular administration of both drugs at 10 µg/25 µl in the contralateral control knee joint provoked a marked synergistic antinociceptive effect indicating significant systemic diffusion through synovial membrane. The oral or intra-articular combination of dexketoprofen and tramadol produced additive or synergistic antinociceptive effects, respectively, in the model of MIA-induced osteoarthritis in rats, that might allow to obtain therapeutic advantages with lower side effects.
authors.affiliation: Department of Pharmacology, Menarini Ricerche S.p.A., via Rismondo 12 A, 50131 Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cialdai
authors.forename: Sandro
authors.initials: S
authors.lastname: Giuliani
authors.forename: Claudio
authors.initials: C
authors.lastname: Valenti
authors.forename: Manuela
authors.initials: M
authors.lastname: Tramontana
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Maggi
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019807:Iodoacetic Acid / Q000009:adverse effects*; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced* / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D014147:Tramadol / Q000008:administration & dosage* / Q000494:pharmacology*; D014325:Tromethamine / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D014325:Tromethamine; D014147:Tramadol; D007660:Ketoprofen; C118296:dexketoprofen trometamol; D019807:Iodoacetic Acid
keywords: Antinociceptive effect; Drug interaction; Incapacitation; Monosodium iodoacetate; Nociception; Osteoarthritis