The Effects Of Chemokine CX3CL1 And CCL21 In Anterior Cingulate Cortex On The Chronic Neuropathic Pain

Background:Chronic neuropathic pain refers to the pain that has been sustained long time since the primary lesion was repaired.Epidemiology showed that 60%of patients with chronic neuropathic pain had pain lasting more than five years.In recent years,chronic neuropathic pain has become an important problem in modem times that plagues human health and the quality of life and life.It is mainly manifested as hyperalgesia and hyperalgesia.Neuropathic pain mechanism is divided into neurogenic inflammatory response,peripheral and central sensitization,changes in neuronal plasticity.The current application of traditional drugs is difficult to effectively control.At present,the study of chronic neuropathic pain is based on the level of spinal cord,the study shows that when the peripheral nerve injury or inflammation,the spinal cord neurons will secrete a variety of proinflammatory cytokines and chemokines,to promote a large number of glial cell activation,activated glial cells will further release the inflammatory mediators and excitatory neurotransmitters,the role of neuronal cells,the neurons in a long period of excitement and abnormal discharge of the state,and then produce chronic neuropathic pain.Verge GM and de Jong et al.found that peripheral neurons in the spinal cord can express chemokines CX3CL1 and CCL21,which can act directly on microglia and promote the activation of microglia,which in turn affects neurons excitement.Trigeminal neuralgia refers to the recurrence of the trigeminal nerve in the sudden short burst of severe pain,but also modem to very common chronic disease pain.The study found that trigeminal neuralgia attack,anterior cingulate cortex(ACC)was activated.This study is focused on the study of trigeminal neuralgia,the anterior cingulate cortex of chemokines CX3CL1,CCL21 for the impact of pain.Abstract Objective:To investigate the effects of chemokine in the anterior cingulate cortex of rat on the chronic neuropathic pain.Methods:A model of trigeminal neuropathic pain was made by chronic constriction injury to the unilateral infraorbital nerve(CCI-ION).100 male Sprague-Dawley rats were randomly assigned into 5 groups(n=20):the sham group;the control group;the PBS treatment group,CX3CL1 antibody treatment group and the CCL21 antibody treatment group.The unilateral infraorbital nerve just be exposed in the sham group;in the control group,we expose unilateral infraorbital nerve firstly,then ligate it.The behavioral tests will be performed at 9 am in the 1,3,5,7,14d after surgery,then execute the rats,take the tissue of ACC to compare the protein expression level of CCL21 SCX3CL1 and CD11b in the three groups.The PBS solution will be injected into ACC at 10:00 am in the day which has the highest level of CCL21 and CX3CL1 expression in the PBS group;The CCL21 neutralizing antibody will be injected into the ACC when having the highest CCL21 expression respectively.The CX3CL1 neutralizing antibody will be injected into the ACC when having the highest CX3CL1 expression respectively.The behavioral tests will be measured 6h later after the injection,then execute the rats,take the tissue of ACC to compare the protein expression level of CCL21 and CD11b of the 2 groups.Results:At baseline,there was no significant difference of feeling threshold among the four groups(P>0.05).Compared with sham-operated rats,there was a significant reduction of the feeling threshold in the ipsilateral territory from 3 to 14 d after unilateral CCI-ION in rats(P<0.05).The feeling threshold of rats given neutralizing antibody has an evident increase compare with the PBS group(P<0.05).Conclusion:The ACC may take part in the chronic neuropathic pain associating with the activated microglial cell and the high-level of CCL21 and CX3CL1 expression.