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Sökning: WFRF:(Belfer Inna)

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1.
  • Bersellini Farinotti, Alex, et al. (författare)
  • Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
  • 2019
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
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2.
  • Neely, G Gregory, et al. (författare)
  • A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
  • 2010
  • Ingår i: Cell. - : Elsevier Science B.V., Amsterdam.. - 0092-8674 .- 1097-4172. ; 143:4, s. 628-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
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3.
  • Skokauskas, Norbert, et al. (författare)
  • The cost of child and adolescent mental health services
  • 2018
  • Ingår i: Lancet psychiatry. - 2215-0374 .- 2215-0366. ; 5, s. 299-300
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • More than 2·5 billion children and adolescents exist worldwide, with most individuals living in low-income and middle-income countries (LMICs).1 For these children and adolescents, mental health and neurodevelopmental disorders remain one of the leading causes of the global burden of disease and years lived with disability.2 Although the importance of child and adolescent mental health (CAMH) has been widely acknowledged by organisations such as the UN,3 the development of an inclusive cross-sectorial mental health system for children and adolescents has not gained adequate traction.
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