Activation of peripheral ephrinBs/EphBs signaling induces hyperalgesia through a MAPKs-mediated mechanism in mice.

Abstract

EphBs receptors and ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Ours and other studies have demonstrated that spinal ephrinBs/EphBs signaling was involved in the modulation of nociceptive information and central sensitization. However, the role of ephrinBs/EphBs signaling in peripheral sensitization is poorly understood. This study shows that intraplantar (i.pl.) injection of ephrinB1-Fc produces a dose- and time-dependent thermal and mechanical hyperalgesia and the increase of spinal Fos protein expression in mice, which can be partially prevented by pre-treatment with EphB1-Fc. EphrinB1-Fc-induced hyperalgesia is accompanied with the NMDA receptor-mediated increase of expression in peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, pERK and pJNK, and also is prevented or reversed by the inhibition of peripheral and spinal MAPKs. Furthermore, in formalin inflammation pain model, pre-inhibition of EphBs receptors by the injection of EphB1-Fc reduces pain behavior, which is accompanied by the decreased expression of peripheral p-p38, pERK and pJNK. These data provide evidence that ephrinBs may act as a prominent contributor to peripheral sensitization, and demonstrate that activation of peripheral ephrinBs/EphBs system induces hyperalgesia through a MAPKs-mediated mechanism.

• Authors: Jun-Li Cao, Jia-Ping Ruan, Di-Yang Ling, Xue-Hai Guan, Qi Bao, Yan Yuan, Li-Cai Zhang, Xue-Jun Song, Yin-Ming Zeng
• Journal: Pain (Pain) Vol. 139 Issue 3 Pg. 617-631 (Oct 31 2008) ISSN: 1872-6623 [Electronic] United States
• PMID: 18706764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Butadienes
• Efnb1 protein, mouse
• Ephrin-B1
• Nitriles
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-fos
• Receptors, N-Methyl-D-Aspartate
• U 0126
• Formaldehyde
• pyrazolanthrone
• Dizocilpine Maleate
• Receptors, Eph Family
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthracenes (pharmacology)
• Butadienes (pharmacology)
• Dizocilpine Maleate (pharmacology)
• Ephrin-B1 (pharmacology, physiology)
• Foot
• Formaldehyde (toxicity)
• Hot Temperature (adverse effects)
• Hyperalgesia (etiology, physiopathology)
• Injections, Spinal
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Nitriles (pharmacology)
• Physical Stimulation (adverse effects)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-fos (analysis)
• Receptors, Eph Family (agonists, physiology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, physiology)
• Spinal Cord (chemistry, physiopathology)
• Touch
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)