Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1

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• 作者：Hitoshi Uchida ; Misaki Matsumoto ; Hiroshi Ueda
• 关键词：Lysophosphatidic acid ; Botulinum toxin C3 ; EphrinB1 ; Neuropathic pain ; Dorsal root ganglion ; Microarray
• 刊名：Neurochemistry International
• 出版年：2009
• 出版时间：March-April 2009
• 年：2009
• 卷：54
• 期：3-4
• 页码：215-221
• 全文大小：476 K

文摘

Lysophosphatidic acid (LPA) signaling, through LPA₁ receptor and its downstream RhoA, has been reported to initiate nerve injury-induced neuropathic pain. In the present study, we performed gene expression profiling of the dorsal root ganglion (DRG) to identify genes induced by intrathecal injection of LPA in a botulinum toxin C3 (BoNT/C3)-reversible manner. We selected and functionally characterized ephrinB1 from 82 identified genes as a potential gene involved in pain transmission, since ephrinB1 is implicated to modulate N-methyl-d-aspartate (NMDA) receptor functions in spinal pain transmission. The LPA-induced and BoNT/C3-reversible ephrinB1 gene expression was confirmed by quantitative real-time PCR. Furthermore, treatments with an antisense oligodeoxynucleotide for ephrinB1 largely abolished the LPA-induced thermal hyperalgesia and allodynia in response to mechanical or Aβ-fiber-mediated electrical stimuli on day 1 after the injection. In addition, intrathecal treatment with a soluble ligand, ephrinB1-Fc, caused similar neuropathic pain-like behaviors in a manner that was reversible by the NMDA receptor antagonist MK-801. These results suggest that ephrinB1 plays a crucial role in LPA-induced neuropathic pain. In addition, the present study may provide a new strategy to identify unique neuropathic pain-related genes.