?7 Nicotinic acetylcholine receptor-mediated anti-inflammatory effect in a chronic migraine rat model via the attenuation of glial cell activation.

ABSTRACT: Background:Evidence suggests that the activation of ?7 nicotinic acetylcholine receptor (?7nAChR) can greatly decrease the neuroinflammation response. Neuroinflammation plays a pivotal role in the pathogenesis of chronic migraine (CM). 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. Materials and methods:Thirty-six male Sprague-Dawley rats were distributed randomly into control, CM, PNU-282987, and ?-bungarotoxin groups (n=9 rats in each group). The CM model was established by the recurrent daily administration of inflammatory soup on the dura over the course of 1 week. The hind paw threshold and facial allodynia were assessed by the von Frey test. The expression levels of ?7nAChR, tumor necrosis factor-alpha, and interleukin-1 beta were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction. The location of ?7nAChR in the hippocampus was quantified by immunofluorescence, as well as the microglial and astrocyte alterations. Changes in the calcitonin gene-related peptide and the phosphorylated JNK protein among different groups were measured by Western blot. Results:We found that the expression of ?7nAChR was reduced after repeated inflammatory soup administration. The increased expression of tumor necrosis factor-alpha, interleukin-1 beta, and calcitonin gene-related peptide in CM group were significantly decreased by PNU-282987 and aggravated by ?-bungarotoxin. Moreover, PNU-282987 decreased the numbers of astrocytes and microglia compared with 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. Activated c-Jun N-terminal kinase signaling was observed in CM rats and was also blocked by PNU-282987. Conclusion:The activation of ?7nAChR increased the mechanical threshold and alleviated pain in the CM rat model. ?7nAChR activation also decreased the upregulation of astrocytes and microglia through the p-c-Jun N-terminal kinase-mitogen-activated protein kinase signaling pathway.

SUBMITTER: Liu Q 

PROVIDER: S-EPMC6007207 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature