The aim of the study was to identify the differential protein expressions related to neuropathic pain and neuroprotection in the dorsal root ganglion (DRG) following chronic compression of DRG (CCD) in rats. We conducted a proteomics study of L(4) and L(5) DRG after CCD for 28 days. A total of 98 protein spots were detected with significant changes in their expression levels after CCD and 15 protein spots were identified by the matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Of these proteins, annexin A2, protein kinase C epsilon (PKCepsilon), glyceraldehyde-3-phosphate dehydrogenases (GAPDH), and heat shock protein 70 (HSP70) were up-regulated significantly compared with the normal control. These four proteins and p11, which was annexin A2 light chain, were further examined by Western blotting. The results of Western blotting and the proteomic analysis showed consistent data. Moreover, real-time quantitative RT-PCR experiments indicated that CCD-induced increase in protein levels was associated with an up-regulation of annexin A2 and PKCepsilon gene expression. In conclusion, this study highlights the molecular process in DRG underlying neuropathic pain. CCD is associated with the up-regulation of annexin A2 and PKCepsilon and their related genes. The up-regulation of GAPDH and HSP70 suggests that there exist concurrent processes of nervous injury and neuroprotection in the course of neuropathic pain.