| Objective:Multiple studies have shown that several nucleus in striatum play a very important role in pain processing and take part in the process of numerous acute or chronic pain diseases.Marginal division of striatum (MrD) is a new functional subdivision in striatum first discovered by domestic scholar. Previous studies have found that there are plenty of nociceptive neurons and substance P which are considered closely related to pain processing in MrD. Recently, Chen Zhiye has reported that a patient with right extremities pain caused by a malacia lesion in the left putamen showed evidently decrease of functional connectivities in the left marginal division when compared to normal controls with the method of resting functional magnetic resonance imaging.In this study, we establish a simulation rat model of chronic migraine (CM) by repetitive inflammatory soup stimulation on superior sagittal sinus dura mater, and then investigate the number and morphological changes of neurons and the expression of substance P in MrD. We also explore the role of MrD in CM disease process in rats by observation that if there are changes of pain perception threshold and behavior in CM model after their MrD have been destroyed.Methods:1. Experiments were performed on male Sprague-Dawley rats (n=72). The rats were randomly divided into six groups:normal saline (NS) control group (n=12), CM group (n=12), CM+bilateral MrD damaged group (n=12), CM+unilateral MrD damaged group (n=12), simple bilateral MrD damaged group (n=12) and simple unilateral MrD damaged group (n=12). CM rat model were established by repetitive inflammatory soup stimulation on superior sagittal sinus dura mater and MrD was destroyed by brain stereotaxic injection of kainic acid.2. Pain perception threshold of rats' periorbital skin was tested by Von Frey filaments and behavior change of the rats was observed by video camera.3. Nissl's staining was used to observe the morphological change of MrD. Immunohistochemical staining was used to investigate the expression of substance P in MrD4. We use immunohistochemical staining method to investigate the expression of c-fos in PAG among different groups and then make quantitative analysis.Results:1. The pain perception threshold of CM group, CM+bilateral MrD damaged group and CM+unilateral MrD damaged group decreased obviously compared with NS control group (P<0.05), there were no significant differences among the above three groups (P>0.05) and there were no significant differences among simple bilateral MrD damaged group, simple unilateral MrD damaged group and NS control group (P>0.05).2. Unilateral grooming and resting behavior increased significantly in CM group, CM+bilateral MrD damaged group and CM+unilateral MrD damaged group while the explore behavior decreased significantly in these groups compared to NS control group (P<0.05). There were no significant differences among simple bilateral MrD damaged group, simple unilateral MrD damaged group and NS control group in all behaviors (P>0.05).3. Nissl's staining showed that there were no changes in the number and morphology of spindle cells in CM group compared with NS control group.4. Immunohistochemical staining of substance P showed that the expression of substance P increased significantly in CM group and CM+unilateral MrD damaged group's undestroyed side of MrD(P<0.05), decreased significantly in CM+bilateral MrD damaged group, simple bilateral MrD damaged group and CM+unilateral MrD damaged group's destroyed side of MrD and simple unilateral MrD damaged group(P<0.05). There was no significant difference between the undestroyed MrD of simple unilateral MrD damaged group compared to NS control group (P>0.05).5. Immunohistochemical staining of c-fos showed that the expression of c-fos increased significantly in CM group,CM+unilateral MrD and CM+bilateral MrD damaged group when compared with NS control group.This can prove that repetitive inflammatory soup stimulation on superior sagittal sinus dura mater can effectively build the rat model of chronic migraine.Conclusion:1. Repetitive inflammatory soup stimulation on superior sagittal sinus dura mater can effectively build the rat model of chronic migraine.2. There were not changes in the number and morphology of neurons in MrD of CM rat, but the expression of substance P increased obviously in MrD of CM rat, which indicated that MrD might be involved in the process of CM disease.3. Destroying MrD of CM rat can't change the pain perception threshold and behavior of rats, which indicated that MrD has no facilitation or inhibition function in the process of CM, the functional change of MrD might be a secondary change in CM. |
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