Reversal of neurochemical changes and pain-related behavior in a model of neuropathic pain using modified lentiviral vectors expressing GDNF.
In this study, we evaluated the possible use of lentiviral vectors in the treatment of neuropathic pain. We chose to administer GDNF-expressing vectors because of the known beneficial effect of this trophic factor in alleviation of neuropathic pain in adult rodents. Lentiviral vectors expressing either GDNF or control, green fluorescent protein or beta-galactosidase, were injected unilaterally into the spinal dorsal horn 5 weeks before a spinal nerve ligation was induced (or sham surgery for the controls). We observed that intraspinally administered lentiviral vectors resulted in a large and sustained expression of transgenes in both neurons and glial cells. Injection of GDNF-expressing viral vectors induced a significant reduction of ATF-3 up-regulation and IB4 down-regulation in damaged DRG neurons. In addition, it produced a partial but significant reversal of thermal and mechanical hyperalgesia observed following the spinal nerve ligation. In conclusion, our study suggests that lentiviral vectors are efficient tools to induce a marked and sustained expression of trophic factors in specific areas of the CNS and can, even if with some limitations, be efficient in the treatment of neuropathic pain.
Pezet
Sophie
S
The London Pain Consortium, Neurorestoration, The Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK. sophie.pezet@kcl.ac.uk
Krzyzanowska
Agnieszka
A
Wong
Liang-Fong
LF
Grist
John
J
Mazarakis
Nicholas D
ND
Georgievska
Biljana
B
McMahon
Stephen B
SB
D051700:Activating Transcription Factor 3 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000494:pharmacology; D006678:HIV / Q000235:genetics; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D037102:Lectins / Q000187:drug effects / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D008026:Ligation; D009437:Neuralgia / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects; D013127:Spinal Nerves / Q000187:drug effects / Q000601:surgery; D014161:Transduction, Genetic
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D037102:Lectins