Effects Of Atorvastatin On CD95/CD95L And Myelin Sheath In Hippocampus Of Rats With Trigeminal Neuralgia

Objective:Research found that there are closely linked between chronic pain and neurodegenerative diseases（Alzheimer’s disease）,neuroinflammation is the bridge that links them,in which CD95/CD95L is a key factor of neuroinflammation in central nervous system.Recent studies have shown that atorvastatin plays a neuroprotective role by reducing neuroinflammation.It was hypothesized that atorvastatin could improve neuropathic pain-induced brain degeneration by inhibiting CD95/CD95L-mediated neuroinflammation.The purpose of this study was to observe:（1）changes in the cognitive function of rats with trigeminal neuralgia and the role of CD95/CD95L;（2）the effect of atorvastatin on pain and cognitive function in rats with trigeminal neuralgia and the role of CD95/CD95L in it.Methods:1.Modeling and interventions:Thirty adult male Sprague Dawley rats were randomly divided into three groups after one week adaptive training:Sham group（Sham group,n=10）,Trigeminal Neuralgia group（dION-CCI group,n=10）,Atorvastain group（ATR group,n=10）.The right infraorbital nerve was dissociated and ligated to induce trigeminal neuralgia.Sham group:the right infraorbital nerve was dissociated,without ligation,and normal saline is given by gavage daily.dION-CCI group:the right infraorbital nerve was dissociated and ligated,and normal saline is given by gavage daily.ATR group:the right infraorbital nerve was dissociated and ligated,and atorvastatin is given by gavage daily.Rats in each group were gavaged continuously for 30 days.2.Detection of pain threshold:Right facial mechanical pain threshold was detected 1 day before modeling and 7^th,14^th,21^th,28^th days after modeling by Von Frey Filament sensory tester.3.Water maze test:Water maze test was started at 5^th before modeling,10^thh and 26^th after modeling,which were recorded as MWM1,MWM2 and MWM3respectively.The escape latency,crossing times of the platform were recorded.4.Detection of CD95/CD95L pathway and downstream inflammatory related factors in hippocampus:At 31^th day after modeling,all rats were sacrificed and the hippocampus was reserved,and the content of CD95,CD95L,NF-κB,IL-1βwere detected by western blotting.5.Detection of myelin basic protein（MBP）in hippocampus:At 31^th day after modeling,all rats were sacrificed,and the content of MBP was detected by western blotting and immunofluorescence in hippocampus.Results:1.Rats models:There were no rats with modeling failure in this experiment,and a total of 30 rats were analyzed in this study.2.Changes in pain threshold:The pain threshold of three groups before modeling was 26g.At 7^th,14^th,21^th,28^th days after modeling,the mechanical pain threshold of dION-CCI group and ATR group were significantly decreased compared to Sham group（P<0.05）.At 14^th,21^th,28^th days after modeling,the mechanical pain threshold of ATR group was significantly increased compared to dION-CCI group（P<0.05）.3.Results of water maze test:There was no statistically significant difference in escape latency and crossing times of the platform in three groups before modeling（MWM1）（P>0.05）.The second water maze test（WMW2）showed no statistically significant difference in escape latency and crossing times of the platform in three groups（P>0.05）.The third water maze test（WMW3）showed a statistically significant difference in escape latency in three groups（P<0.05）:compared to Sham group,the escape latency was prolonged in dION-CCI group（P<0.05）,but ATR group showed no significant difference in the escape latency（P>0.05）;compared to dION-CCI group,the escape latency was shortened in ATR group（P<0.05）;There was no significant difference in crossing times of the platform in three groups（P>0.05）.4.Changes in expression of CD95/CD95L pathway and inflammatory related factors downstream in hippocampus:Compared to Sham group,the expression of CD95,CD95L,NF-κB,IL-1βin dION-CCI group were increased（P<0.05）.Compared to Sham group,the expression of CD95,CD95L,NF-κB,IL-1βwere no statistically significant difference in ATR group（P>0.05）.Compared to dION-CCI group,the expression of CD95,CD95L,NF-κB,IL-1βin ATR group were decreased（P<0.05）.5.Changes in expression of myelin basic protein（MBP）in hippocampus:Compared to Sham group,the expression of MBP in dION-CCI group was decreased（P<0.05）.Compared to Sham group,the expression of MBP was no statistically significant difference in ATR group（P>0.05）.Compared to dION-CCI group,the expression of MBP in ATR group was increased（P<0.05）.Conclusion:1.The decrease of learning ability in rats with trigeminal neuralgia may be related to increased expression of CD95,CD95L,NF-κB,IL-1βin hippocampus and demyelination of hippocampal neurons.2.Atorvastain treatment lead to pain relief,improved the learning ability and improved demyelination of hippocampal neurons in rats with trigeminal neuralgia.The mechanism relevant to its effect on suppressing CD95,CD95L,NF-κB,and IL-1β,so that to inhibition neuroinflammation in hippocampus.