Cancer-Induced Bone Pain Sequentially Activates the ERK/MAPK Pathway in Different Cell Types in the Rat Spinal Cord

Autor: Hao Cheng, Yan Peng, Yan-bing Zhang, Qi-nian Xu, Cai-fang Li, Ming Yao, Lina Wang, Jianping Yang, Jianling Zuo, Xiu-yun Wang, Fu-hai Ji, Jun Peng
Rok vydání: 2011
Předmět:
MAPK/ERK pathway
medicine.medical_specialty
MAP Kinase Signaling System
Pain
Bone Neoplasms
Pharmacology
Rats
Sprague-Dawley
Cellular and Molecular Neuroscience
Internal medicine
Nitriles
lcsh:Pathology
Butadienes
medicine
Animals
extracellular signal-regulated protein kinase (ERK)
rat
Citrates
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Bone pain
Injections
Spinal
hyperalgesia
Analgesics
Tibia
Microglia
business.industry
Research
MEK inhibitor
spinal cord
Nerve injury
Spinal cord
Rats
Enzyme Activation
Radiography
Anesthesiology and Pain Medicine
Endocrinology
medicine.anatomical_structure
Nociception
Organ Specificity
Hyperalgesia
Molecular Medicine
bone cancer pain
cAMP response element-binding protein (CREB)
medicine.symptom
business
lcsh:RB1-214
Zdroj: Molecular Pain
Molecular Pain, Vol 7, Iss 1, p 48 (2011)
ISSN: 1744-8069
DOI: 10.1186/1744-8069-7-48
Popis: 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.
Databáze: OpenAIRE
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