Molecular effects of interleukin-1β on dorsal root ganglion neurons: Prevention of ligand-induced internalization of the bradykinin 2 receptor and downregulation of G protein-coupled receptor kinase 2

Banchet, Gisela Segond von; Fischer, Nadja; Uhlig, Benjamin; Hensellek, Susanne; Eitner, Annett; Schaible, Hans‐Georg

doi:10.1016/j.mcn.2010.09.009

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…Based on these findings, we believe that patients could benefit from a transient pharmacological reduction of sympathetic activation at acute inflammatory stages and during RA exacerbations. Such treatment is also likely to reduce the inflammatory pain because hyperalgesia is most severe in the acute stage,29–32 and, as shown here, sympathectomised AIA mice had significantly less hyperalgesia than AIA control mice.…”

Section: Discussionsupporting

confidence: 55%

The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses

et al. 2011

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Section: Discussionsupporting

confidence: 55%

The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses

et al. 2011

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“…Such a down‐regulatory effect would also explain the reduction in the extent of heat‐induced hyperalgesia, which is again consistent with the interpretation that IL‐1β and IL‐1 receptors have an important function in thermal hyperalgesia. Furthermore, blockade of the IL‐1β effects may also attenuate, indirectly, the nociceptive effects of inflammatory mediators on neurons, because IL‐1β increases the responsiveness of multiple G protein–coupled receptors through down‐regulation of G protein–coupled receptor kinase 2, thus supporting the concept of inflammatory mediators having nociceptive actions on neurons (34–36).…”

Section: Discussionmentioning

confidence: 93%

The role of interleukin‐1β in arthritic pain: Main involvement in thermal, but not mechanical, hyperalgesia in rat antigen‐induced arthritis

Ebbinghaus¹,

Uhlig²,

Richter³

et al. 2012

Arthritis & Rheumatism

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106

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Objective. Interleukin-1␤ (IL-1␤) is considered a pronociceptive cytokine, but its role in the generation of arthritic pain is unknown. The aim of this study was to investigate the role of IL-1␤ in arthritic pain and to explore the antinociceptive potential of the IL-1 receptor type I (IL-1RI) antagonist anakinra.Methods. Antigen-induced arthritis (AIA) was induced in rats. Expression of IL-1RI in the dorsal root ganglia (DRGs) was determined, and the effects of anakinra on inflammation, pain-related behavior, and receptor expression were assessed. In cultured DRG neurons, the effect of IL-1␤ on the expression of the transient receptor potential vanilloid 1 (TRPV-1) ion channel was examined. Recordings of action potentials from joint nociceptors were made after intraarticular injection of IL-1␤ into the rat knee joints.Results. AIA generated pronounced and persistent mechanical and thermal hyperalgesia, and IL-1RI expression in the lumbar DRGs was significantly upregulated. Treatment with anakinra did not significantly reduce the severity of arthritis or mechanical hyperalgesia, but did result in a pronounced reduction in thermal hyperalgesia. In cultured DRG neurons, IL-1␤ up-regulated the expression of TRPV-1, a major transduction molecule involved in thermal hyperalgesia.During AIA, anakinra treatment down-regulated the expression of TRPV-1, consistent with the pronounced reduction in thermal hyperalgesia. IL-1␤ increased the mechanosensitivity of C-fibers of the joint, but reduced the mechanosensitivity of A␦-fibers, thus having opposite effects on these mechanonociceptive nerve fibers.Conclusion. In the context of arthritic knee pain, IL-1␤ and IL-1 receptors appear to be involved in thermal, rather than mechanical, hyperalgesia. Therefore, neutralization of IL-1␤ may be mainly antinociceptive in disease states characterized by thermal hyperalgesia, but not in disease states mainly characterized by mechanical hyperalgesia.

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“…Incubation of DRG neurons with IL-1β for several days produced excitatory effects typified by a reduced threshold for depolarization in a subpopulation of DRG neurons [19], and downregulated G protein-coupled receptor kinase 2, thus increasing the responsiveness of multiple G protein– coupled receptors (GPCR) on DRG neurons [20]. Exposure of naïve DRG neurons to IL-1β over two days also resulted in upregulated expression of TRPV1, suggesting a mechanism by which IL-1 may participate in the persistence of thermal hyperalgesia in inflammatory states [21].…”

Section: Nociceptive Actions Of Cytokinesmentioning

confidence: 99%

Osteoarthritis joint pain: The cytokine connection

2014

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Osteoarthritis is a chronic and painful disease of synovial joints. Chondrocytes, synovial cells and other cells in the joint can express and respond to cytokines and chemokines, and all of these molecules can also be detected in synovial fluid of patients with osteoarthritis. The presence of inflammatory cytokines in the osteoarthritic joint raises the question whether they may directly participate in pain generation by acting on innervating joint nociceptors. Here, we first provide a systematic discussion of the known proalgesic effects of cytokines and chemokines that have been detected in osteoarthritic joints, including TNF-α, IL-1, IL-6, IL-15, IL-10, and the chemokines, MCP-1 and fractalkine. Subsequently, we discuss what is known about their contribution to joint pain based on studies in animal models. Finally, we briefly discuss limited data available from clinical studies in human osteoarthritis.

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Molecular effects of interleukin-1β on dorsal root ganglion neurons: Prevention of ligand-induced internalization of the bradykinin 2 receptor and downregulation of G protein-coupled receptor kinase 2

Cited by 14 publications

References 37 publications

The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses

The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses

The role of interleukin‐1β in arthritic pain: Main involvement in thermal, but not mechanical, hyperalgesia in rat antigen‐induced arthritis

Osteoarthritis joint pain: The cytokine connection

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