title: Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection.
abstract: OBJECTIVE
  The Rho GTPase, Rac1, is involved in the pathogenesis of neuropathic pain induced by malformation of dendritic spines in the spinal dorsal horn (sDH) neurons. In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied.
  
  
  METHODS
  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-activated kinase (PAK), ERKs and p38 MAPK in inflammatory pain states was evaluated with a pull-down assay and Western blotting. The preventive and therapeutic analgesic effects of intrathecal administration of NSC23766, a selective inhibitor of Rac1, on BV-induced spontaneous nociception and pain hypersensitivity were investigated.
  
  
  RESULTS
  Rac1 labelling was mainly localized within neurons in both the superficial and deep layers of the sDH in rats of naïve, vehicle-treated and inflamed (BV injected) groups. GTP-Rac1-PAK and ERKs/p38 were activated following s.c. BV injection. Post-treatment with intrathecal NSC23766 significantly inhibited GTP-Rac1 activity and phosphorylation of Rac1-PAK, ERKs and p38 MAPK in the sDH. Both pre-treatment and post-treatment with intrathecal NSC23766 dose-dependently attenuated the paw flinches, primary thermal and mechanical hyperalgesia and the mirror-image thermal hyperalgesia induced by BV injection, but without affecting the baseline pain sensitivity and motor coordination.
  
  
  CONCLUSIONS
  The spinal GTP-Rac1-PAK-ERK/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.
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Li
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.affiliation: School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Guan
authors.affiliation: Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.|Beijing Institute for Brain Disorders, Beijing, 100069, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D059787:Acute Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001514:Bee Venoms; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D017628:Microglia / Q000378:metabolism; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D000700:Analgesics; D001514:Bee Venoms; C487513:NSC 23766; D011743:Pyrimidines; D054462:p21-Activated Kinases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein