Abstract:
BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: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. KEY 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 AND IMPLICATIONS: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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Wang Y,Lu YF,Li CL,Sun W,Li Z,Wang RR,He T,Yang F,Yang Y,Wang XL,Guan SM,Chen Jdoi
10.1111/bph.13413subject
Has Abstractpub_date
2016-03-01 00:00:00pages
937-50issue
5eissn
0007-1188issn
1476-5381journal_volume
173pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:The thiazolidine carboxylic acid, BML-241, has been proposed as a lead compound in development of selective antagonists at the sphingosine-1-phosphate receptor (S1P3), based on its inhibition of the rise in intracellular calcium concentrations ([Ca2+]i) in HeLa cells overexpressing S1P receptors....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706872
更新日期:2006-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13297.x
更新日期:1995-03-01 00:00:00
abstract::1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pm...
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doi:10.1038/sj.bjp.0702255
更新日期:1998-12-01 00:00:00
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更新日期:2006-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08406.x
更新日期:1977-10-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1986.tb14596.x
更新日期:1986-04-01 00:00:00
abstract::1. The effect of mastoparan on phosphatidylcholine hydrolysis was examined in 1321N1 human astrocytoma cells. Mastoparan (3-30 microM) caused an accumulation of diacylglycerol (DG) and phosphatidic acd (PA) accompanied by choline release in a concentration- and time-dependent manner. 2. In the presence of 2% n-butanol...
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更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0702112
更新日期:1998-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701482
更新日期:1997-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15651.x
更新日期:1996-08-01 00:00:00
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更新日期:2020-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09560.x
更新日期:1970-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14324.x
更新日期:1992-06-01 00:00:00
abstract::1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15950.x
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更新日期:2004-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-02-01 00:00:00
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更新日期:2011-05-01 00:00:00
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doi:10.1111/j.1476-5381.1992.tb13421.x
更新日期:1992-12-01 00:00:00
abstract::1. Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular effects not only by preventing the formation of angiotensin II (AII), but also by promoting the accumulation of bradykinin in or at the vessel wall. In addition, certain ACE inhibitors have been shown to augment the vasodilator response to br...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701281
更新日期:1997-08-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1996-05-01 00:00:00
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pub_type: 社论
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更新日期:2011-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12483
更新日期:2014-02-01 00:00:00
abstract::1. We previously showed that chronic exposure to aspirin (100 mg kg-1 daily, by mouth) is effective in preventing the onset of hypertension in young (28-84 day old) spontaneously hypertensive rats (SHRs). This is contrary to what others have reported using older SHRs. 2. Renal prostaglandin F2 alpha was also reduced i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11585.x
更新日期:1988-07-01 00:00:00
abstract::1 Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum. The ID50 for the enzyme, purified from pig antrum mucosa by ultracentrifugation and chromatography on DEAE-cellulose, was 2.5 muM. 2 In six dogs with Heidenhanin pouches th...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb06934.x
更新日期:1975-11-01 00:00:00