Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

نویسندگان

  • Li-na Wang
  • Ming Yao
  • Jian-ping Yang
  • Jun Peng
  • Yan Peng
  • Cai-fang Li
  • Yan-bing Zhang
  • Fu-hai Ji
  • Hao Cheng
  • Qi-nian Xu
  • Xiu-yun Wang
  • Jian-ling Zuo
چکیده

BACKGROUND Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed activation of spinal cells and the ERK/MAPK pathway in a rat model of bone cancer pain. RESULTS A Sprague Dawley rat model of bone cancer pain was established and the model was evaluated by a series of tests. Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK inhibitor) was administered intrathecally. Western blots and double immunofluorescence were used to detect the expression and location of phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time between day 6 and day 18 is a reasonable period ("time window" as the remaining stages) to investigate bone cancer pain mechanisms and to research analgesic drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK) and the transcription factor cAMP response element-binding protein (p-CREB) increased in the spinal cord of CIBP rats, which was attenuated by intrathecal injection of fluorocitrate or U0126. CONCLUSIONS The ERK inhibitors could have a useful role in CIBP management, because the same target is expressed in various cells at different times.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

MiR-103 alleviates autophagy and apoptosis by regulating SOX2 in LPS-injured PC12 cells and SCI rats

Objective(s): Recent studies revealed that microRNAs (miRNAs) may play crucial roles in the responses and pathologic processes of spinal cord injury (SCI). This study aimed to investigate the effect and the molecular basis of miR-103 on LPS-induced injuries in PC12 cells in vitro and SCI rats in vivo. Materials and Methods: PC12 cells were exposed to LPS to induce cell injuries to mimic the in ...

متن کامل

BIOINFORMATIC STUDY ON EFFECT OF XANTHOHUMOL AS BIOACTIVE COMPOUND OF HOP IN THE INHIBITION OF THE MAPK/ERK PATHWAY IN THYROID CANCER

Background: Xanthohumol is one of the main bioactive compounds extracted from the female flowers of the hops plant (Humulus lupulus L), that has been shown in several studies to have anti-cancer effects.The MAPK/ERK pathway is one of the key pathways in the regulation of gene expression, cell growth and survival. The abnormal activation of this pathway leads to the uncontrolled cell proliferati...

متن کامل

Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis

Objective(s): Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in β-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat. Materials and Methods: We used three-month-...

متن کامل

Central Neuropathic Pain After Graft of Bone Marrow Stromal Cells in the Spinal Cord Contusion of Rat

Purpose: The purpose of this study was the investigation of thermal and mechanical Allodynia after BMSCs grafting in the Spinal Cord Contusion of rat Materials and Methods: In this study used 40 female Sprague- Dawley 6-8 week old that 33 rats received vertebral laminectomy to expose spinal cord (L1 vertebral level). The cord was then contused with the weight drop device. Experimental groups c...

متن کامل

P183: Key Function of Complement System in Interactions between Pain and Nociceptors, C5a, and C3a

A part of the immune system that improves (complements) the ability of antibodies and phagocytic cells to clear microorganisms and injured cells from an organism, attacks the pathogen's cell membrane, and encourages inflammation called complement system. It is main part of immune system. Over thirty proteins and protein pieces compose the complement system, including cell membrane receptors, an...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2011