Effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinol on neuropathic pain in rat model of L5 spinal nerve ligation / 临床麻醉学杂志

ABSTRACT

Objective To explore the effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinolon on hyperalgesia in a rat model of L5 spinal nerve ligation and its underlying mechanism. Methods After lumber intrathecal catheters implanted,90 male Sprague-Dawley rats (40-50 d,weighing 180-220 g)were randomly divided into six groups (n=15 each)Naive group (group N),Sham operation group (group S),SNL group (group C)and three Garcinol treatment groups (group H500μg/kg,group M100μg/kg,group L20μg/kg).Group N did not receive any operation in rats.In group S,the L5 spinal nerve was only exposed without ligation.Other four groups all received spinal nerve ligation (SNL).Group N,group S and group SNL were administrated intrathcelly with 100% DMSO (10 μl)within 3 to 6 days after SNL surgery.Other three groups were treated with Garcinol 500μg/kg (group H),100μg/kg (group M),20 μg/kg (group L)at the same points respectively.Behaviorally,thermal withdrawal latency (TWL) were measured at 1 day (T0 )before and on days 1(T1 ),3(T2 ),5(T3 ),7(T4 ),9(T5 ),11(T6 ),14(T7 )after surgery separately.On the 7th day after behavioral testing,the lumber segment of the spinal cord was removed to test the level of p300 and acetyl-p65 by western blot,while NF-κB was detected with immunofluorescence. Results Compared with group N,TWL was significantly shortened in group C,L,M and H,the levels of ace-tyl-p65 and p300 in group C,L,M and H were markedly increased,the expression of NF-κB in group C,L,M and H was markedly increased(P<0.05).Compared with group C,TWL was significantly prolonged in group M and group H,the levels of acetyl-p65 and p300 in group M and group H were dramatically decreased,the expression of NF-κB in group H was obviously decreased(P <0.05).Conclusion The acetyltransferase p300 inhibitor Garcinol imposes protective effect in SNL-induced neuropathic pain.Mechanisms are probably associ-ated with decreasing acetyl-p65 protein expression level in the NF-κB pathway.