The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats.
BACKGROUND
Cyclin-dependent kinase 5 (Cdk5) has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) via the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway in the dorsal horn of the spinal cord in rats.


RESULTS
Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine.


CONCLUSIONS
Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF/TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF/TrkB signaling cascade may present a potential target for anti-inflammatory pain.
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China ; Department of Anesthesiology, Hang Zhou First People's Hospital, Nan Jing Medical University, Zhejiang, P. R. China.
Hong-Hai
HH
Zhang
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Xiao-Qin
XQ
Zhang
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Qing-Sheng
QS
Xue
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Yan-Luo
Department of Pharmacy, Sixth Affiliated Hospital of Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Jin-Lu
JL
Huang
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Su
S
Zhang
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Hai-Jun
HJ
Shao
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Han
H
Lu
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Wen-Yuan
WY
Wang
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
Bu-Wei
BW
Yu
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077546:Roscovitine; D015398:Signal Transduction; D013116:Spinal Cord
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D005620:Freund's Adjuvant; C049985:staurosporine aglycone; D020813:Receptor, trkB; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat