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EphrinBs/EphBs signaling is involved in modulation of spinal nociceptive processing through a mitogen-activated protein kinases-dependent mechanism
- Source :
- Anesthesiology. 112(5)
- Publication Year :
- 2010
-
Abstract
- Background Our previous studies have demonstrated that EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. The aim of this study was to further investigate whether mitogen-activated protein kinases (MAPKs), as the downstream effectors, participate in modulation of spinal nociceptive information related to ephrinBs/EphBs. Methods Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filaments test. Immunofluorescence staining was used to detect the expression of p-MAPKs and of p-MAPKs/neuronal nuclei, or p-MAPKs/glial fibrillary acidic protein double label. C-Fos expression was determined by immunohistochemistry. The expression of p-MAPKs was also determined by Western blot assay. Results Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal p-MAPKs and c-Fos expression. Immunofluorescence staining revealed that p-MAPKs colocalized with the neuronal marker (neuronal nuclei) and the astrocyte marker (glial fibrillary acidic protein). Inhibition of MAPKs prevented and reversed pain behaviors and the increase of spinal c-Fos expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. Furthermore, pretreatment with MK-801, an N-methyl-d-aspartate receptor antagonist, prevented behavioral hyperalgesia and activation of spinal MAPKs induced by intrathecal injection of ephrinB1-Fc. Conclusions These results demonstrated that activation of MAPKs contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.
- Subjects :
- Male
MAP Kinase Signaling System
Pain
Ephrin-B1
Mice
Nitriles
medicine
Butadienes
Animals
Injections, Spinal
Pain Measurement
Receptors, Eph Family
biology
Glial fibrillary acidic protein
business.industry
Spinal cord
Cell biology
Anesthesiology and Pain Medicine
Nociception
Allodynia
medicine.anatomical_structure
Hyperalgesia
Mitogen-activated protein kinase
Immunology
biology.protein
medicine.symptom
Signal transduction
Inflammation Mediators
Mitogen-Activated Protein Kinases
business
Astrocyte
Subjects
Details
- ISSN :
- 15281175
- Volume :
- 112
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Anesthesiology
- Accession number :
- edsair.doi.dedup.....e95eedd4a0476c256ba0280e4476a19a