Abstract: Purpose: Neuropathic pain has defined as Pain resulting from injury or disease of the somatosensory nervous system. Neurons biochemically Are consistent to Reduction and increased activity, that this Biochemical changes could affect the Maintenance and survival of neurons. consideration to regulatory role of Cdk5 in the function and structure of the nervous, the end of this study was The effect of 6 weeks decreased activity in the form of spinal cord ligation on CDK5 expression in sciatic nerve of Wistar male rats with neuropathic pain Materials and methods: ten adult male Wistar rats in the weight range of 250±20 gr, randomly were divided into two groups including healthy control (C), ligation (SNL). Over the six weeks neuropathic pain behavior tests were conducted continually in groups. In the end change of CDK5 gene expression in sciatic nerve was measured with Real time technique and calculated using the 2-ΔΔCT method. Results: after 6 weeks Soleus muscle weight was significantly decreased in ligation group compared to control group (p<0.05). in the behavioral tests of neuropathic pain was shown pain threshold was significantly lower than in ligation group compare to control group (p<0.05). CDK5 gene expression in sciatic nerve increased significantly (pathologically) in ligation group related to control group (p<0.05). Conclusion: It seems that after a period of decreased activity in the form of spinal cord ligation, pathological Increase of CDK5 gene expression can leads to destructive effect on the neuromuscular system and emerge of pathological markers such as neuromuscular atrophy, acceleration of apoptosis and neurodegenerative disease.