Available online at www.annclinlabsci.org Intrathecal Transplantation of Neural Stem Cells Appears to Alleviate Neuropathic Pain in Rats Through Release of GDNF

Abstract. The beneficial effect of stem cells on several animal models of neuropathic pain has been recog-nized recently. However, there have been no studies on the effects of neural stem cell transplantation on neuropathic pain. In the present study, using the rat model of chronic constriction injury of the sciatic nerve, we observed the effect of intrathecal transplantation of extrinsic neural stem cells on the behavior and expression of neurotrophins such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the spinal dorsal horn and dorsal root ganglia (DRG), and analyzed BDNF and GDNF protein levels secreted by neural stem cells in vitro before and after differentiation. We found that intrathecal administration of neural stem cells 3 days after injury could significantly attenuate mechanical and thermal hyperalgesia. Furthermore, real-time PCR and enzyme-linked immunosorbent assay (ELISA) results together showed that the expression of GDNF, rather than BDNF, was significantly elevated in the neural stem cell transplantation group. The in vitro ELISA results showed that after dif-ferentiation, GDNF secrection was dramatically increased, whereas BDNF expression was sharply down-regulated. We therefore concluded that the secretion of GDNF, but not BDNF, by the transplanted neural stem cells might contribute to the relief of neuropathic pain. Key words: neural stem cell; chronic constrction injury; spinal dorsal horn; glial cell line-derived neuro-trophic factor; brain-derived neurotrophic facto