title: Evidence that LPS-reactive arthritis in rats depends on the glial activity and the fractalkine-TNF-α signaling in the spinal cord.
abstract: It is known that primary afferent central terminal sensitization can influence peripheral inflammation, however, it remains to be understood whether spinal cord glia can also contribute to this process. Our aim was to investigate the effect of spinal cord glia inhibition on the pathogenesis of LPS-induced knee-joint monoarthritis in rats and also to investigate the role of fractalkine and TNF-α. LPS was injected into the knee-joint previously primed with carrageenan to cause articular incapacitation, edema, synovial leukocyte infiltration, and GFAP and CD11b/c spinal immunoreactivity (glia-IR) increase. Articular edema was more sensitive to the inhibition by intrathecal fluorocitrate and minocycline than nociception and synovial leukocyte content. The higher doses of both drugs were ineffective when given by intraperitoneal route. Corticosteroid synthesis inhibition by aminoglutethimide did not change the glia inhibitors effect. The inhibitory effect of the dorsal root potential inhibitor, furosemide, was not additive to that caused by fluorocitrate and minocycline. Intrathecal anti-fractalkine and anti-TNF-α inhibited edema, nociception, and synovial leukocytes, while fractalkine caused the opposite effects. The fractalkine effect was inhibited by fluorocitrate and anti-TNF-α. Finally, fluorocitrate, minocycline and anti-fractalkine attenuated, but fractalkine increased, GFAP and CD11b/c IR. The evidence reported herein supports the hypothesis that spinal fractalkine release is involved in glia activation, which via the spinal release of TNF-α, seems to be involved in the development and maintenance of this arthritis model. A possible modulation of the dorsal root reflexes is discussed. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors: Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Trindade, Florianópolis, Santa Catarina 88040-900, Brazil.
authors: Elisângela
authors: E
authors: Bressan
authors: Kaite Cristiane
authors: KC
authors: Peres
authors: Carlos Rogério
authors: CR
authors: Tonussi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016918:Arthritis, Reactive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology / Q000627:therapeutic use; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D054428:Chemokine CX3CL1; D002951:Citrates; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C007744:fluorocitrate; D008911:Minocycline