Effect of preemptive local injection of ropivocaine with dexmedetomidine on mirror pain in rats and its mechanism

Objective:To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.Methods:A total of 48 adult male Sprague-Dawley rats(weighing 180 g-220 g)were included in the study and randomized into 3 groups,Group S,Group R,and Group RD,.A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups.Before procedures and nerve extraction,Group S(n=16)was injected 0.9%saline locally;Group R(n=16)was injected 0.5%ropivocaine locally,and Group RD,(n=16)was injected 0.5%ropivocaine in combined with 1μg dexmedetomidine locally.After the model being established in the three groups,8 rats were used for behavior test until 28 d,and dorsal root ganglions(DRGs)of the other 8 rats were harvested on the3 rd day after surgery.Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG,and the behavior test results in the three groups were compared.Results:The results showed that mechanical pain threshold in ipsilateral hindpaws of the Group S,Group R,Group RD,animals dropped to(3.640±1.963)g,(5.827±1.204)g,(7.482)±1.412 g at 3 d respectively;while in contralateral paws dropped to(7.100±1.789)g,(17.687±1.112)g,(16.213±1.345)g on the 3 d respectively.Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups,but ipsilateral paws expressed more active glial cells than contralateral paws.Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws,but Group RD,formula could reduce glial cells activity,mitochondria swelling/vacuolization and the amount of lysosomes.Conclusions:Local injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG,mitigate the pathological changes of neuron in DRG and reduce mirror image pain.

Discovery of novel double pyrazole Schiff base derivatives as anti-tobacco mosaic virus(TMV) agents

Many pyrazole derivatives were reported to exhibit highly activity towards tobacco mosaic virus（TMV）.In this work,an optimized pyrazole Schiff base scaffold was designed and introduced to derive novel potential TMV inhibitors.Thirty-six compounds were synthesized,characterized by elemental analysis,mass spectra and nuclear magnetic resonance（NMR） spectroscopy and evaluated by biological experiments.The bioassay results showed that some of the synthesized compounds exhibited excellent anti-TMV activities.Especially,5-chloro-3-methyl-1H-pyrazole contained compound 4j showed ningnanmycin comparable inhibitory activity and can be considered as potential anti-TMV candidate agent.With molecular docking,compound 4j insert into nucleotide sequence（GAAGUU） of OriRNA stably which revealed nucleotide could be a target of these compounds.