title: Tumour necrosis factor-alpha mediates carrageenin-induced knee-joint incapacitation and also triggers overt nociception in previously inflamed rat knee-joints.
abstract: Tumour necrosis factor-alpha (TNF alpha) was studied in the carrageenin (CG) induced knee-joint incapacitation, and also in mediating recurrent incapacitation response in knee-joints previously exposed to an inflammatory attack. CG or TNF alpha intra-articular injection into CG-primed knee-joints induced an intense and long-lasting (>8 h) peaking incapacitation response. TNF alpha injected in naive joints did not elicit incapacitation. Anti-TNF alpha serum in situ treatment specifically inhibited CG-induced incapacitation in naive joints, and also TNF alpha-induced incapacitation in primed joints. Hoe-140 (D-Arg0[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin, a bradykinin B2 receptor antagonist, given before CG, abolished incapacitation, but was without effect when injected 3 h after. Hoe-140 given before or after the CG injection in primed joints was without effect, but it produced a partial inhibitory effect in the early phase (1 h) of TNF alpha-induced incapacitation. Des-Arg9[Leu3]-bradykinin, a bradykinin B1 receptor antagonist, given intra-articularly after CG or TNF alpha, reversed incapacitation either in naive or primed joints. Indomethacin abolished the incapacitation induced by CG in naive joints, but only the 5-lipoxygenase inhibitor MK-886 plus indomethacin blocked the response in primed joints. MK-886 did not modify CG-induced incapacitation in naive joints, but lately reversed CG-induced incapacitation in primed joints, and blocked TNF alpha-induced response. Substance P or prostaglandin E2 did not induce incapacitation in either naive or primed joints. Our results support the conclusion that TNF alpha is a mediator of CG-induced inflammatory incapacitation, and is able to induce the further release of kinins and leukotrienes, which is suggested to have an important role in the maintenance of long-lasting nociceptive response.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tonussi
authors.forename: Sérgio H
authors.initials: SH
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001168:Arthritis / Q000139:chemically induced*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002351:Carrageenan; D015232:Dinoprostone / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects*; D008297:Male; D010146:Pain / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D002351:Carrageenan; D015232:Dinoprostone; D001920:Bradykinin