Ameliorative Effect Of Escin On Pain In Rats With Trigeminal Neuralgia

Objective Trigeminal neuralgia is a kind of refractory neuropathic pain in oral and maxillofacial region.At present,the main treatment of trigeminal neuralgia is drug therapy,and the preferred drug is the anticonvulsant drug like carbamazepine.However,because of the occurrence of dose-dependent and related complications when such drugs are used for a long time,and the analgesic effect is weakened with the extension of medication time,it is necessary to find alternative drugs.In this research,through the study of trigeminal neuralgia rat model,the therapeutic effect of a potential drug escin on trigeminal neuralgia was investigated,and the possible mechanism of escin in the process of analgesia was preliminary explored.Methods Chronic constriction of the infraorbital nerve（CCI-ION）was used to establish the model of trigeminal neuralgia in rats.Grouping of animals: SD rats were randomly divided into Sham group,CCI-ION group,CCI-ION + carbamazepine group,low-dose escin group,medium-dose escin group and high-dose escin group.Intragastric administration was started on the day of surgical model preparation,and the daily dose of carbamazepine in the positive control group was 42mg/kg.In the experimental group,the daily dosage of low,medium and high doses of escin were 6mg/kg,12mg/kg and24mg/kg respectively.Sham group and CCI-ION group were given the equivalent dose of saline every day for 14 consecutive days.Behavioral test: Mechanical pain threshold of rats was measured by Von Frey fiber filaments before operation（day 0）and on day 3,5,7 and 14 after operation,and the effects of different drug interventions on pain were compared.On the 14 th day of operation,the experimental rats were sacrificed and the trigeminal ganglion of the operative side was removed.Molecular biological detection:RT-PCR was used to detect m RNA expression of TNF-α,IL-1β,TLR4 and NF-κB in trigeminal ganglion.Histopathological examination: hematoxylin-eosin staining was used to observe the pathological conditions of trigeminal ganglion,such as myelin changes,schwann cell number changes and inflammatory cell infiltration under light microscope,then evaluated the degree of nerve injury.Results Behavioral test results showed that compared with Sham group,mechanical pain threshold of rats in CCI-ION group decreased significantly on the 3rd day after surgery（n=6,P<0.01）,the pain effect lasted until the 14 th day after surgery,indicating that trigeminal neuralgia model was successfully established.Compared with CCI-ION group,the mechanical pain threshold of rats in each administration group began to increase gradually on day 3 of administration,and significantly increased on day 5 in carbamazepine group,medium-dose and high-dose escin groups（n=6,P<0.01）;mechanical pain threshold was significantly increased in the carbamazepine group and escin group at all levels of dose on day 7 and 14（n=6,P<0.01）.Compared with Sham group,the expression levels of TNF-α,IL-1β,TLR4 and NF-κB m RNA in CCI-ION group were significantly increased（n=4,P<0.01）;Compared with CCI-ION group,m RNA expression of TNF-α,IL-1β,TLR4 and NF-κB in all treatment groups were significantly decreased（n=4,P<0.05）.Histopathological results showed that compared with Sham group,inflammatory cell’s infiltration,schwann cell number’s increase and demyelination’s changes were observed in TG group under light microscope.Compared with the CCI-ION group,the inflammation of TG in the carbamazepine group and escin groups at all levels of dose was reduced to different degrees under the light microscope.Conclusion Escin has a certain ameliorative effect on trigeminal neuralgia induced by CCI-ION,and the mechanism may be related to the down-regulation of pro-inflammatory cytokine release,which plays a role through TLR-4/NF-κB signaling pathway.