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Effects of Vitamin B12 Combined with Lamotrigine on CREB/BDNF Pathway and Neurological Dysfunction in Rats with Trigeminal Neuralgia |
XIA Kehe, LI Wei |
The People's Hospital of Inner Mongolia Autonomous Region, Inner Mongolia Hohhot 010000, China |
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Abstract Objective: To investigate the effects of vitamin B12 combined with lamotrigine on cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway and neurological dysfunction in rats with trigeminal neuralgia. Methods: The rat models of trigeminal neuralgia were established by chronic constriction injury of infraorbital nerve (ION-CCI). The models were divided into model group, drug group and drug + H89 group, and the sham operation group was treated with corresponding treatment, with 12 rats in each group. In the drug group, lamotrigine and vitamin B12 were given intramuscular injection; in drug + H89 group, 5μL CREB pathway inhibitor H89 was injected into lateral ventricle on the basis of drug group; the rats in the sham operation group and model group were intramuscularly injected with and orally taken the same volume of normal saline, for 15 days. The mechanical pain threshold and the frequency of face scratching were measured before and 1st, 3rd, 5th, 7th, 9th, 11th, 13th, 15th day after modeling; the morphology of semilunar ganglion and hippocampus was observed by scanning electron microscope; Western blot was used to detect the protein levels of p-CREB, CREB and BDNF pathway in semilunar ganglion and hippocampus. Results: Before modeling, there was no significant difference in the mechanical pain threshold and the frequency of grasping the face (P>0.05); after modeling, the mechanical pain threshold and the frequency of face scratching in model group, drug group and drug + H89 group were significantly increased (P<0.05), and with the extension of time, the mechanical pain threshold decreased and the number of face grabbing decreased first and then increased in the model group, the mechanical pain threshold and the frequency of face scratching gradually stabilized to a certain level in the drug group, the condition of drug + H89 group was between model group and drug group. On the 15th day of modeling, the semilunar ganglion in the model group was significantly damaged, the number of nerve fibers decreased, and some neurons in the hippocampus showed obvious vacuolar degeneration, the number of mitochondria decreased and the volume swelling; in the drug group, the semilunar ganglion was significantly improved, the vacuolar degeneration of hippocampal neurons and the swelling degree of mitochondria were reduced; in the drug + H89 group, the structure of semilunar ganglion was blurred, and there were still serious vacuolar degeneration and a serious decrease in the number of mitochondria in the hippocampus. Compared with those in the sham operation group, the protein levels of p-CREB/CREB and BDNF in semilunar ganglion and hippocampus in model group were decreased (P<0.05); compared with those in the model group, the protein levels of p-CREB/CREB and BDNF in the semilunar ganglion and hippocampus in the drug + H89 group were increased (P<0.05); compared with those in the drug group, the protein level of BDNF in semilunar ganglion and the protein level of p-CREB/CREB in semilunar ganglion and hippocampus were decreased in drug + H89 group (P<0.05). Conclusion: Vitamin B12 combined with lamotrigine can effectively improve neurological dysfunction, activate CREB/BDNF pathway and protect trigeminal neuralgia rats.
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