Several molecular changes occur following axotomy, such as gene up-regulation and down-regulation. In our previous study using Affymetrix arrays, it was found that after the axotomy of sciatic nerve, there were many novel genes with significant expression changes. Among such genes was neuronatin, whose expression was significantly up-regulated. Neuronatin was identified as a gene selectively expressed in the neonatal brain and is involved in neuronal differentiation during brain development, and markedly reduced in adult brains. The present study investigated whether the expression of neuronatin correlates with symptoms of neuropathic pain in adult rats with transected sciatic nerve. Adult male Sprague-Dawley rats weighting 230 to 280 g were used. The rats were grouped into two: those that were sham operated and those that had sciatic nerve axotomy. The specimens-L4,5 dorsal root ganglians(DRG) and their corresponding spinal cords-were collected at post-axotomy day 1, day 3, and day 5. The neuronatin protein contents were analyzed by western blotting and immunohisto- chemistry. Changes in the mRNA levels were evaluated using RT-PCR. Randall and Selitto test was performed to reveal changes in the animal behaviors. The subcellular co-localization of neuronatin with neuronal cell type specific markers were also investigated in correlation with pain-related animal behavior. It was found that after sciatic nerve injury, the expression of neuronatin in dorsal root ganglians was increased in protein extracts. Furthermore, the results of immunohistochemistry revealed that the cell numbers of DRGs were relatively increased. Unmyelinated C-fiber and thinly myelinated A-£_ fiber in adult DRGs were also among the principal sub-population of primary afferent neurons with distributed neuronatin. The increased expression of neuronatin and its subcellular localization were related to mechanical hyperalgesia. The results indicated that there was a following significant correlation between mechanical allodynia axotomy of sciatic nerve and the increased expression of neuronatin in C-fiber and A-£_ fiber of DRG neurons.