• Hideo Kobayashi, Takuya Kitamura, Miho Sekiguchi, Miwako K Homma, Yukihito Kabuyama, Shin-ichi Konno, Shin-ichi Kikuchi, and Yoshimi Homma.
• Department of Orthopaedic Surgery and Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima, Japan.
• Spine. 2007 Jul 1;32(15):1592-8.

Study DesignWe investigated involvement of EphB/ephrinB system in neuropathic pain.ObjectiveUsing immunoblotting, immunohistochemistry, and RNA interference techniques, we examined the expression levels of EphB receptors and ephrinB ligands in neuropathic pain. We also explored the effect of ephrinB siRNA for neuropathic pain.Summary Of Background DataIt has been reported that EphB2 regulates the development of synaptic plasticity in the hippocampus by interacting with N-methyl-D-aspartate (NMDA) receptors. In acute pain models, it has been clear that EphB1/ephrinB2 interactions via the NMDA receptor modulates synaptic efficacy in spinal cord.MethodsAdult female Sprague-Dawley rats were used in this study. A crush injury model was prepared by crushing the left L5 spinal nerve distal to dorsal root ganglions (DRG) under deep anesthesia. The sham operation was subjected as control. Expression of ephrinB2 and EphB1 were examined by immunoblotting and immunohistochemical analyses with anti-EphB and anti-ephrinB antibodies. To assess involvement of ephrinB in neuropathic pain, we examined the effect of small interference RNA (siRNA) on mechanical allodynia.ResultsAmong EphB and ephrinB isoforms tested, ephrinB2 and EphB1 were predominant in DRG and spinal cord. Results showed that the expression of ephrinB2 was enhanced in neurons in DRG and spinal cord by the injury in a time-dependent manner. EphB1 was expressed in neurons of spinal cord. Administration of ephrinB2 siRNA reduced the expression of ephrinB2 and mechanical allodynia.ConclusionExpression of ephrinB2 is enhanced by nerve injury in neurons in DRG and spinal cord, while its receptor EphB1 is expressed in spinal cord. These results suggest that induction of ephrinB2 might activate EphB1/ephrinB2 signaling pathway to regulate synaptic plasticity and reorganization, and that ephrinB2 siRNA could be a potential therapeutic agent for neuropathic pain.

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