[cAMP response-element binding protein participates in the phosphorylated extracellular signal-regulate kinase mediated neuropathic pain].
It has been reported that extracellular signal-regulate kinase (ERK) is involved in the modulation of nociceptive information and central sensitization produced by intense noxious stimuli and/or peripheral tissue inflammation. Few studies have explored the relationship between ERK and cAMP response-element binding protein (CREB) in neuropathic pain after nerve injury, such as chronic constriction injury (CCI) of the sciatic nerve. In the present study, CCI model was employed to investigate the activation of ERK on the expression of phosphorylated CREB (pCREB) in chronic neuropathic pain. Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at around 1.0- mm intervals with 4-0 silk suture. Mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered one day before and three consecutive days after CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and von Frey filaments respectively. The expression of pCREB and Fos were assessed by both Western blot and immunohistochemical analysis. The results showed that intrathecal injection of U0126 or ERK antisense ODN attenuated significantly CCI-induced mechanical and thermal hyperalgesia. Correlating with behavior results, the injection also markedly suppressed the increase of CCI-induced pCREB and c-Fos expression. The results obtained suggest that CREB participates in the pERK-mediated neuropathic pain.
Song
Xue-Song
XS
Department of Anesthesiology, First Clinical College of N. Bethune Centre Health Sciences, Jilin University, Changchun 130021, China.
Xu
Yan-Bing
YB
Cao
Jun-Li
JL
He
Jian-Hua
JH
Zhang
Li-Cai
LC
Zeng
Yin-Ming
YM
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases