Neuronal cell death may be responsible for the pathogenesis of neuropathic pain. Glial cell line-derived neurotrophic factor (GDNF) protects sensory neurons after injury and offers a promising alternative for the management of intractable pain. However, continuous administration of trophic factors into the central nervous system is costly and difficult to maintain. Therefore, we evaluated the potential of intrathecal GDNF gene delivery for the treatment of neuropathic pain. Recombinant adenovirus encoding GDNF (Ad-GDNF) was characterized and shown to enhance viability of neuronal cultures. After intrathecal injection of Ad-GDNF, an elevated GDNF level was observed in spinal cord for four weeks. In rats with sciatic nerve axotomy,intrathecal injection of Ad-GDNF significantly ameliorated the duration of neuropathic pain. However, animals treated with Ad-GDNF developed hyperalgesia in the early stage of treatment. Immunofluorescence analysis indicated that intrathecal GDNF gene delivery prominently attenuated the neuronal loss due to nerve injury. Unexpectedly, varying degrees of hair loss was found in some rats receiving Ad-GDNF. Histological analysis revealed that hair loss resulted from severe degeneration of hair follicles in skin from Ad-GDNF-treated animals. In summary, the present study demonstrate the feasibility and limitations of GDNF gene delivery for the management of neuropathic pain.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0714103-155007 |
| Date | 14 July 2003 |
| Creators | Wu, Ping-Ching |
| Contributors | Ming-Hong Tai, Jau-Cheng Liou, Lin-Cheng Yang, Hung-Tu Huang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0714103-155007 |
| Rights | unrestricted, Copyright information available at source archive |
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