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The aim of this study was to explore the potential role and mechanisms of\n                      <jats:styled-content style=\"fixed-case\">SOC<\/jats:styled-content>\n                      channels in collagen\u2010induced arthritis (\n                      <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>\n                      mouse model was used to examine the effects of the\n                      <jats:styled-content style=\"fixed-case\">SOC<\/jats:styled-content>\n                      channel inhibitor YM\u201058483 on\n                      <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>\n                      and arthritic pain. Hargreaves' and von Frey hair tests were conducted to measure thermal and mechanical sensitivities of hind paws.\n                      <jats:sc>elisa<\/jats:sc>\n                      was performed to measure cytokine production, and haematoxylin and eosin staining was used to assess knee histological changes.\n                      <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>\n                      estern blot analysis was performed to examine protein levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Pretreatment with 5 or 10\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      of\n                      <jats:styled-content style=\"fixed-case\">YM<\/jats:styled-content>\n                      \u201058483 reduced the incidence of\n                      <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>\n                      , prevented the development of inflammation and pain hypersensitivity and other signs and features of arthritis disease. Similarly, treatment with\n                      <jats:styled-content style=\"fixed-case\">YM<\/jats:styled-content>\n                      \u201058483 after the onset of\n                      <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>\n                      : (i) reversed the clinical scores; (ii) reduced paw oedema; (iii) attenuated mechanical and thermal hypersensitivity; (iv) improved spontaneous motor activity; (v) decreased periphery production of\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20101\n                      <jats:styled-content style=\"fixed-case\">\u03b2<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20106 and\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">\u03b1<\/jats:styled-content>\n                      ; and (vi) reduced spinal activation of\n                      <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n                      and calmodulin\u2010dependent\n                      <jats:styled-content style=\"fixed-case\">PKII<\/jats:styled-content>\n                      (\n                      <jats:styled-content style=\"fixed-case\">CaMKII\u03b1<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      This study provides the first evidence that inhibition of\n                      <jats:styled-content style=\"fixed-case\">SOC<\/jats:styled-content>\n                      entry prevents and relieves rheumatoid arthritis (\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      ) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of\n                      <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">CaMKII\u03b1<\/jats:styled-content>\n                      in the spinal cord. These results suggest that\n                      <jats:styled-content style=\"fixed-case\">SOC<\/jats:styled-content>\n                      channels are potential drug targets for the treatment of\n                      <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13104","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T02:06:54Z","timestamp":1423102014000},"page":"2991-3002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A store\u2010operated calcium channel inhibitor attenuates collagen\u2010induced arthritis"],"prefix":"10.1111","volume":"172","author":[{"given":"X H","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine Philadelphia PA 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