| Background:Chronic migraine(chronic migraine,CM)seriously affect the patient's physical and mental health,resulting in a loss of productivity,reduced quality of life and a large consumption of medical resources.Due to the high morbidity,the World Health Organization(WHO)listed CM as one of the most four chronic disabled functional disorders.Neuroinflammation plays a pivotal role in the pathogenesis of chronic migraine(CM).Suppression of neuroinflammation can decrease the hyperpathia in CM.Evidence suggests that the activation of ?7 nicotinic acetylcholine receptor(?7nAChR)can greatly decrease the neuroinflammation response.Nicotine can active a7naChR,clinical observations also show that nicotine gum induces analgesic effects in migraine patients.However,whether ?7nAChR is involved in CM is unclear.Objective:To investigate the role of ?7nAChR in CM and provide a new therapeutic target for CM.Methods:Thirty-six male Sprague-Dawley rats were distributed randomly into control,CM,PNU-282987 and a-bungarotoxin groups(n=9 rats in each group).The CM model was established by the recurrent daily administration of inflammatory soup(IS)on the dura over the course of one week.Vernicle PBS,PBS,PNU-282987(?7 agonist),?-Bungarotoxin(a7 antagonist)were administered by intracerebroventricular(I.C.V.)injection on eighth day.The hind paw threshold and facial allodynia were assessed by the von Frey test.The expression levels of a7nAChR,Tumor necrosis factor-?(TNF-?)and Interleukin-1 ?(IL-1?)were analyzed by western blotting(WB)and quantitative real time polymerase chain reaction(qRT-PCR).The location of ?7nAChR in the hippocampus were quantified by immunofluorescence,as well as the astrocyte and microglial alterations.Results:We found that the expression of a7nAChR was reduced after repeated IS administration.The activation of a7nAChR increased the mechanical threshold and alleviated pain in the CM rat model.The increased expression of TNF-?,IL-1? and CGRP in CM group were significantly decreased by PNU-282987 and aggravated by ?-Bungarotoxin.Moreover,PNU-282987 decreased the numbers of astrocytes and microglia compared to the numbers in the CM group in both hippocampal CA1 and CA3 regions.In contrast,?-bungarotoxin activated the astrocytes and microglia,but the differences with respect to the CM group were not significant.Conclusion:The activation of ?7nAChR decreased the upregulation of astrocytes and microglia,reduced the production of TNF-? and IL-1?,and inhibited neuroinflammation in CM. |
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