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In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Effects of s.c. bee venom (BV) injection on cellular localization of Rac1 in the rat sDH was determined with double labelling immunofluorescence. Activation of Rac1 and its downstream effector p21\u2010activated kinase (PAK), ERKs and p38 MAPK in inflammatory pain states was evaluated with a pull\u2010down assay and <jats:styled-content style=\"fixed-case\">Western blotting<\/jats:styled-content>. The preventive and therapeutic analgesic effects of intrathecal administration of NSC23766, a selective inhibitor of Rac1, on BV\u2010induced spontaneous nociception and pain hypersensitivity were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Rac1 labelling was mainly localized within neurons in both the superficial and deep layers of the sDH in rats of na\u00efve, vehicle\u2010treated and inflamed (BV injected) groups. GTP\u2010Rac1\u2010PAK and ERKs\/p38 were activated following s.c. BV injection. Post\u2010treatment with intrathecal NSC23766 significantly inhibited GTP\u2010Rac1 activity and phosphorylation of Rac1\u2010PAK, ERKs and p38 MAPK in the sDH. Both pre\u2010treatment and post\u2010treatment with intrathecal NSC23766 dose\u2010dependently attenuated the paw flinches, primary thermal and mechanical hyperalgesia and the mirror\u2010image thermal hyperalgesia induced by BV injection, but without affecting the baseline pain sensitivity and motor coordination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The spinal GTP\u2010Rac1\u2010PAK\u2010ERK\/p38MAPK signalling pathway is involved in both the development and maintenance of peripheral inflammatory pain and can be used as a potential molecular target for developing a novel therapeutic strategy for clinical pain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13413","type":"journal-article","created":{"date-parts":[[2015,12,24]],"date-time":"2015-12-24T04:12:46Z","timestamp":1450930366000},"page":"937-950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection"],"prefix":"10.1111","volume":"173","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Biomedical Sciences of Pain, Tangdu Hospital The Fourth Military Medical University  Xi'an 710038 China"},{"name":"Institute for Functional Brain Disorders, Tangdu Hospital The Fourth Military Medical University  Xi'an 710038 China"},{"name":"Key Laboratory of Brain Stress and Behavior, PLA  Xi'an 710038 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