Activation of transcription factor c-jun in dorsal root ganglia induces VIP and NPY upregulation and contributes to the pathogenesis of neuropathic pain.
Vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in dorsal root ganglia (DRGs) are known to be upregulated and to contribute to the mechanisms of neuropathic pain following peripheral nerve injury. Moreover, transcription factor c-Jun regulates the expressions of both VIP and NPY in cultured DRG neurons. To elucidate the role of c-Jun in the induction of neuropathic pain hypersensitivity, we examined whether activated c-Jun affects pain behavior and the expressions of VIP and NPY following chronic constriction injury (CCI) of rat sciatic nerve. Intrathecal treatment with c-jun antisense oligodeoxynucleotides (AS-ODN) significantly reduced mechanical allodynia, but not thermal hyperalgesia following CCI. In addition, c-jun AS-ODN also suppressed the remarkable elevations of VIP and NPY mRNAs and the percentages of phosphorylated c-Jun-, VIP-, and NPY-immunoreactive neurons observed in DRGs following CCI. These results show that the activation of c-Jun in DRGs induces VIP and NPY upregulation and contributes to the pathogenesis of neuropathic pain following CCI.
Son
Sun-Joo
SJ
Department of Anatomy, School of Medicine, Kyungpook National University, 2-101, Dongin Dong, Daegu 700-422, South Korea.
Lee
Kyung-Min
KM
Jeon
Sang-Min
SM
Park
Eun-Sung
ES
Park
Kwon-Moo
KM
Cho
Hee-Jung
HJ
D000818:Animals; D003251:Constriction, Pathologic; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006358:Hot Temperature; D006987:Hypesthesia / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009437:Neuralgia / Q000209:etiology*; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010812:Physical Stimulation; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013997:Time Factors; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
D009478:Neuropeptide Y; D016376:Oligonucleotides, Antisense; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide