title: Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat.
abstract: Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked pain behaviors. We hypothesized that QUIS-induced inflammation and subsequent gene expression contribute to the development and progression of pain-related behaviors and that blockade of inflammation-related gene expression leads to the amelioration of these behaviors. Using the QUIS model of spinal cord injury, we examined whether interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is able to reduce mRNA levels of inflammatory and cell death-related genes leading to a reduction of pain behaviors. The results demonstrate that animals receiving systemic injection of IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), CD95 ligand (CD95-L, also called FAS-L/APO-1L), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results of QUIS injury plus IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS mRNA and these results were supported by Western blot analysis of protein levels following IL-10 treatment. These data suggest that IL-10 reduces inflammation and that targeting injury-induced inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Plunkett
authors.forename: C G
authors.initials: CG
authors.lastname: Yu
authors.forename: J M
authors.initials: JM
authors.lastname: Easton
authors.forename: J R
authors.initials: JR
authors.lastname: Bethea
authors.forename: R P
authors.initials: RP
authors.lastname: Yezierski
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051546:Cyclooxygenase 2; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006120:Grooming / Q000187:drug effects; D006801:Humans; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010146:Pain / Q000503:physiopathology*; D010841:Pia Mater; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D016318:Quisqualic Acid / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000503:physiopathology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505655:Tnfsf10 protein, rat; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016318:Quisqualic Acid; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases