title: Antihyperalgesic effect of pentoxifylline on experimental inflammatory pain.
abstract: The antihyperalgesic effect of pentoxifylline was investigated in three experimental pain models. Pentoxifylline (0.5-1.6 mg kg(-1)) given 30 min before the stimulus significantly inhibited the writhing response induced by the intraperitoneal (i.p.) administration of either acetic acid (-90%) or zymosan (-83%), but not that of iloprost, in mice, as well as the zymosan-induced articular hyperalgesia in the zymosan arthritis in rats (-50%). Pentoxifylline also inhibited the mechanical hypernociception in rats induced by the intraplantar injection of either carrageenin (-81%), bradykinin (-56%) or tumor necrosis factor alpha (TNF-alpha; -46%), but not that induced by interleukin-1beta (IL-1beta) or prostaglandin E(2) (PGE(2)). Pentoxifylline did not inhibit the nociceptive response in the hot plate test in mice. Further, the antinociceptive effect of pentoxifylline in the writhing test in mice and the zymosan-induced articular hyperalgesia were not reversed by the coadministration of the opioid receptor antagonist naloxone. Thus, pentoxifylline antinociceptive effect is probably not mediated at a central level. Pentoxifylline significantly reduced TNF-alpha (-43%) and IL-1beta (-42%) concentrations in the joint exudates of rats stimulated by intra-articular injection of zymosan and the production of both cytokines (-66 and -86%, respectively) by mouse peritoneal macrophages stimulated in vivo with zymosan as well as the expression of TNF-alpha at the tissue level in carrageenin-injected rat paws. In conclusion, the antinociceptive activity of pentoxifylline is associated with the inhibition of the release of both TNF-alpha and IL-1beta.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel, Nunes de Melo, 1127, CEP 60430-270, Fortaleza, CE, Brazil.
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Vale
authors.forename: Verônica M
authors.initials: VM
authors.lastname: Benevides
authors.forename: Daniela
authors.initials: D
authors.lastname: Sachs
authors.forename: Gerly A C
authors.initials: GA
authors.lastname: Brito
authors.forename: Francisco A C
authors.initials: FA
authors.lastname: da Rocha
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Sérgio H
authors.initials: SH
authors.lastname: Ferreira
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
mesh_terms: D019342:Acetic Acid; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology; D002351:Carrageenan; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D016285:Iloprost; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007375:Interleukin-1 / Q000096:biosynthesis; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan
chemical_list: D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D015054:Zymosan; D016285:Iloprost; D019342:Acetic Acid; D010431:Pentoxifylline