{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:05:49Z","timestamp":1791907549479,"version":"4.3.4"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T00:00:00Z","timestamp":1278979200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T00:00:00Z","timestamp":1278979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Interleukin-6 (IL-6) is a key player in systemic arthritis, involved in inflammation and joint destruction. IL-6 signalling has also been revealed in nerve cells. Recently, IL-6 and in particular IL-6 together with its soluble IL-6 receptor (sIL-6R) were shown to induce a long-lasting robust sensitization of joint nociceptors for mechanical stimuli which was difficult to reverse, suggesting that IL-6 signalling plays a significant role in the generation and maintenance of arthritic pain. Here we tested in a preclinical model of arthritis, antigen-induced arthritis (AIA) in the rat, whether systemic or local neutralization of IL-6\/sIL-6R complexes with soluble glycoprotein 130 (sgp130) alters arthritic pain and how sgp130 influences the inflammatory process in AIA.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Rats with AIA were either treated with sgp130 or saline intra-peritoneally or intra-articularly (each group n = 9). Then, pain-related and locomotor behaviour, as well as joint swelling, were measured during an observation period of 21 days, followed by histopathological end-point analysis for inflammatory and destructive changes.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>A single intra-articular application of sgp130 at the time of AIA induction barely reduced the development of AIA, but significantly attenuated pain-related behaviour, that is, primary mechanical hyperalgesia in the acute phase of AIA. By contrast, repeated systemic application of sgp130 after onset of AIA only slightly attenuated pain at a late stage of AIA. None of the treatments reduced secondary hyperalgesia. Furthermore, in the present study joint destruction at 21 days was significantly attenuated after intra-articular sgp130 treatment, but not after systemic sgp130.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>In addition to its role in chronic inflammation, IL-6 in the joint plays a significant role in the generation and maintenance of arthritic joint pain at acute and chronic stages of AIA. The particular effectiveness of intra-articular injection of sgp130 indicates, first, that IL-6\/sIL-6R in the inflamed joint, rather than circulating IL-6\/sIL-6R, is responsible for the generation of hyperalgesia, and, second, that early neutralization of IL-6\/sIL-6R is particularly successful in producing antinociception. Furthermore, neutralization of IL-6\/sIL-6R (and possibly other cytokines which use the transmembrane signal-transducing subunit gp130) directly at the site of joint inflammation seems to be effective in the prevention of joint destruction.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3079","type":"journal-article","created":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T18:14:20Z","timestamp":1279044860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis"],"prefix":"10.1186","volume":"12","author":[{"given":"Michael K","family":"Boettger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Leuchtweis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"K\u00fcmmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczyslaw","family":"Gajda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Br\u00e4uer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Schaible","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,13]]},"reference":[{"key":"2914_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.autrev.2009.01.012","volume":"8","author":"JE Fonseca","year":"2009","unstructured":"Fonseca JE, Santos MJ, Canhao H, Choy E: Interleukin-6 as a key player in systemic inflammation and joint destruction. 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