Analgesic effect of angiotensin angiotensin Ⅱ type 2 receptor antagonist EMA401 on neuropathic pain in rats and its mechanism / 中国病理生理杂志

ABSTRACT

AIM:To explore whether angiotensin Ⅱtype 2 receptor antagonist EMA 401 decreases neuropathic pain and the expression of growth-associated protein-43 (GAP-43), protein kinase C (PKC) and calmodulin (CaM) in dorsal root ganglia (DRG) during chronic constriction injury (CCI) in rats.METHODS:SD rats were used to establish CCI model and randomly divided into 4 groups.The rats in model group were given equal volume of normal saline by intra-gastric administration .The rats in low dose ( LD) group were given 5 mg/kg EMA401 by intragastric administration .The rats in middle dose ( MD) group were given 10 mg/kg EMA401 by intragastric administration .The rats high dose ( HD) group were given 20 mg/kg EMA401 by intragastric administration .The rats in sham operation group received equal volume of normal saline by intragastric administration .Thermal withdrawal latency ( TWL ) and mechanical withdrawal threshold (MWT) were measured before operation and 7 d, 14 d and 28 d after CCI.After behavioral test, DRG of lumbar spinal was obtained from each group , and was used to determine Ca 2+concentration by o-cresolphthalein complexone microplating method, and the expression of GAP-43, PKC and CaM at mRNA and protein levels by Western blotting and RT-PCR.RE-SULTSCompared with model group, EMA401 significantly increased the TWL and MWT (P <0.05).Meanwhile, EMA401 significantly reduced Ca 2+concentration and the expression of GAP-43, PKC and CaM at mRNA and protein levels in the DRG (P<0.05).CONCLUSION:EMA401 may attenuate neuropathic pain of CCI by inhibiting Ca 2+concentra-tion and the expression of GAP-43, PKC and CaM.