【Abstract】 Objective Through the detection of calcitonin gene related peptide (calcitonin gene related peptide, CGRP) and adenosine 2A receptor (adenosine 2A, receptor, A2AR) protein expression in the trigeminal nerve tissue of migraine model rats to investigate the role of CGRP and A2AR in the pathogenesis of migraine in rats. Methods 30 male SpragueDawley (SD) rats were randomly divided into control group and model group, 15 rats in each group. Migraine model without aura was established. The rats in the model group were subcutaneously injected with nitroglycerin, which was administered 1 times a week for 5 weeks. The control group was injected with saline instead of nitroglycerin. Behavioral scores were scored on two groups of rats. Then we collected two groups of rat skull base trigeminal ganglia. The expression of CGRP in the trigeminal ganglion was detected by immunohistochemistry, and the expression of A2AR in the trigeminal ganglion was detected by immunofluorescence method. The expression ofA2AR protein was detected by Western blot method.Results The model group and the control group showed normal distribution of neurons and nerve fibers, no disturbance, complete anatomical structure, and no abnormal change. The expression of A2AR protein and gray level in model group were higher than those in control group (P＜001). In the model group, the expression of A2AR in the trigeminal nerve neurons was significantly more than that in the control group. The number of positive neurons in the model group expressing A2AR was higher than that in the control group (P＜001). The expression level of CGRP in the model group and was significantly higher than the control group (P＜001).Conclusion There were no anatomical changes in the trigeminal nerve tissue during the migraine attack in the model rats. The behavioral changes of rats are related to the dysfunction of trigeminal nerve. Expression of A2AR activation or protein upregulation, and mass release of CGRP.A2AR and CGRP may play an important role in the pathogenesis of migraine.