Effects Of Bupivacaine Subarachnoid Block On The NR2B/CaMK??/CREB Signaling Pathway In Rat Spinal Cord

Objective N-methyl-D-aspartate receptor 2B subunit/calcium-calmodulin-dependent protein kinase ? ?/cAMP response element-binding protein(NR2B/CaMK??/CREB)signaling pathway plays an important role in regulating the inflow of peripheral noxious stimulation to supraspinal regions.This study is to investigate the effects of intrathecal bupivacaine on the NR2B/CaMK??/CREB signaling pathway.Materials and methods Spinal effects of bupivacaine injection in rats was tested by a hot tail flick test.A rat subarachnoid block model was established and then 0.5% bupivacaine was injected,and the tail flick time of a rat was detected at each interval by 5 minutes,and the time was observed until 65 min after the bupivacaine injection.The relationship between sedation of subarachnoid block and NR2B/CaMK? ? /CREB signaling pathway: 36 rats were randomly assigned into saline and bupivacaine groups.Each rat intrathecally received 20?l of either normal saline or 0.5% bupivacaine.The expression levels of the NR2 B,CaMK??/p-CaMK??,and CREB/p-CREB in the lumbar spinal cord were detected by Western blot,quantitative real-time RT-PCR,and immunohistochemical(IHC)and then the data was analyzed.Results After subarachnoid injection,bupivacaine took effect immediately,reached the maximum effect within 5 minutes,it began to decay after 30 minutes and reached the level before administration of 60 minutes.The western blot analysis showed that protein expressions of NR2 B,p-CaMK??,and p-CREB in the spinal cord were reduced,in comparison with NS groups.Similar changes in expression were observed by IHC analysis.The mRNA expression levels of NR2 B,CaMK??,and CREB were also down-regulated after bupivacaine intrathecal administration.Conclusion The sedative effect of bupivacaine subarachnoid blockade is possibly due to deafferentation,which might reduce the cortical arousal via down-regulation of spinal NR2B/CaMK??/CREB pathway in vivo.