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The main objective of this study was to investigate the protective effect of glial cell line\u2013derived neurotrophic factor (GDNF) using peripheral gene delivery in a rat model of constriction-induced peripheral nerve injury. In this study, it was shown that mechanical and thermal hypersensitivity increased on the injured limb at day 7 after chronic constrictive injury (CCI) was induced. The neurological changes were correlated with the structural changes and loss of GDNF\/Akt signaling, particularly in the distal stump of the injured sciatic nerve. Subsequently, recombinant adenovirus was employed to evaluate the potential of intramuscular GDNF gene delivery to alleviate the CCI-induced nerve degeneration ad neuropathic pain. After CCI for 3 days, intramuscular injection of adenovirus encoding GDNF (Ad-GDNF) restored the protein level and activity of GDNF\/Akt signaling pathway in the sciatic nerve. This was associated with an improved myelination profile and behavioral outcomes in animals with CCI. In conclusion, the present study demonstrates the involvement of GDNF loss in the pathogenesis of CCI-induced neuropathic pain and the therapeutic potential of intramuscular GDNF gene delivery for the treatment of peripheral nerve degeneration.<\/jats:p>","DOI":"10.1089\/hum.2010.036","type":"journal-article","created":{"date-parts":[[2011,5,23]],"date-time":"2011-05-23T17:06:37Z","timestamp":1306170397000},"page":"721-731","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Glial Cell Line\u2013Derived Neurotrophic Factor Gene Transfer Exerts Protective Effect on Axons in Sciatic Nerve Following Constriction-Induced Peripheral Nerve Injury"],"prefix":"10.1177","volume":"22","author":[{"given":"Jhih-Yin","family":"Shi","sequence":"first","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guei-Sheung","family":"Liu","sequence":"additional","affiliation":[{"name":"Kaohsiung Veterans General Hospital","place":["Taiwan"]},{"name":"University of Melbourne","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"I-Shou University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiao-Mei","family":"Kuo","sequence":"additional","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cha-Hwa","family":"Ton","sequence":"additional","affiliation":[{"name":"Kaohsiung Veterans General Hospital","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Hong","family":"Wen","sequence":"additional","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Tee","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Kaohsiung Veterans General Hospital","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Tu","family":"Huang","sequence":"additional","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chao","sequence":"additional","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hong","family":"Tai","sequence":"additional","affiliation":[{"name":"National Sun Yat-Sen University","place":["Taiwan"]},{"name":"Kaohsiung Veterans General Hospital","place":["Taiwan"]},{"name":"National Sun Yat-Sen University","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,10,18]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn812"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb44735.x"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.124"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00183-3"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00430.x"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.10.036"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-23-08754.2000"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2005.16.4.303"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm850"},{"key":"e_1_3_3_11_1","first-page":"E3","article-title":"The role of neurotrophic factors in nerve regeneration. 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