Down-regulation of GFRalpha-1 expression by antisense oligodeoxynucleotide aggravates thermal hyperalgesia in a rat model of neuropathic pain.
Glial cell line-derived neurotrophic factor (GDNF) has been hypothesized to play an important role in the modulation of nociceptive signals especially during neuropathic pain. The present study examined the expression of GDNF and GFRalpha-1 (the high-affinity receptor of GDNF) in dorsal root ganglions (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. In order to address the role of GDNF and GFRalpha-1 in neuropathic pain, antisense oligodeoxynucleotide (ODN) specifically against GFRalpha-1 was intrathecally administered to result in down-regulation of GFRalpha-1 expression. The results showed that both the protein and mRNA levels of GDNF and GFRalpha-1 were significantly increased after CCI, while the thermal hyperalgesia of neuropathic pain rats could be significantly aggravated by antisense ODN treatment, but not by normal saline (NS) or mismatch ODN treatment. The present study demonstrated that endogenous GDNF and GFRalpha-1 might play an anti-hyperalgesic role in neuropathic pain of rats. In addition, we found a down-regulation of somatostatin (SOM) in DRG and spinal dorsal horn after expression of GFRalpha-1 was knocked down, which suggested the possible relationship between the anti-hyperalgesic effect of GDNF and GFRalpha-1 on neuropathic pain and endogenous SOM.
Dong
Zhi-Qiang
ZQ
Department of Integrative Medicine and Neurobiology, Institute of Acupuncture Research, Shanghai Medical College, Fudan University, China.
Wang
Yan-Qing
YQ
Ma
Fei
F
Xie
Hong
H
Wu
Gen-Cheng
GC
D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000473:pathology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics*; D006930:Hyperalgesia / Q000235:genetics* / Q000473:pathology; D008297:Male; D009437:Neuralgia / Q000235:genetics* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D020133:Reverse Transcriptase Polymerase Chain Reaction
C511536:GRFalpha-1 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger