c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensitivity.
Inflammatory pain, characterized by a decrease in the nociceptive threshold, arises through the actions of inflammatory mediators. Mitogen-activated protein kinase cascades participate in peripheral nociceptive sensitization. We examined the involvement of c-Jun N-terminal kinase (JNK) in the dorsal root ganglion (DRG) in the early phase of inflammation-induced hyperalgesia. An intra-plantar (i.pl.) injection of complete Freund's adjuvant induced the activation of JNK in DRG neurons within 30 min. Pre-treatment as well as post-treatment of rats with a JNK inhibitor, SP600125, significantly attenuated thermal hyperalgesia, as assessed by paw-withdrawal latency, and the upregulation of c-fos immunoreactivity in dorsal horn neurons. An i.pl. injection of nerve growth factor (NGF) also induced the phosphorylation of JNK as well as thermal hyperalgesia, and SP600125 improved hyperalgesia. Inhibitor experiments suggest that JNK and extracellular signal-regulated protein kinase act on primary nociceptive neurons synergistically. These findings demonstrate that JNK is a therapeutic target for treating inflammation-induced pain hypersensitivity.
Doya
Hideo
H
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Ohtori
Seiji
S
Fujitani
Masashi
M
Saito
Tomoko
T
Hata
Katsuhiko
K
Ino
Hidetoshi
H
Takahashi
Kazuhisa
K
Moriya
Hideshige
H
Yamashita
Toshihide
T
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006930:Hyperalgesia / Q000201:enzymology; D007249:Inflammation / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010146:Pain / Q000201:enzymology*; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013696:Temperature
D000873:Anthracenes; C432165:pyrazolanthrone; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases