内田 仁司、松本 みさき、植田 弘師
Profiling of pain-related genes induced by lysophosphatidic acid, an initiator of neuropathic pain
Hitoshi Uchida, Misaki Matsumoto, Hiroshi Ueda
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences
Recently, we have demonstrated that lysophosphatidic acid receptor (LPA1) signaling through RhoA activation initiates 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 RhoA inhibitor botulinum toxin C3 (BoNT/C3)-reversible manner. We identified a total of 283 genes that were up-regulated by LPA treatment. Further analysis showed that, among the 283 putatively up-regulated genes, 82 genes expression were reversed by BoNT/C3, while BoNT/C3 itself had no effect on their expression levels. We selected 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. Treatments with an antisense oligodeoxynucleotide for ephrinB1 largely abolished the LPA-induced thermal hyperalgesia and allodynia. In addition, intrathecal treatment with a soluble ligand, ephrinB1-Fc, caused similar neuropathic pain-like behaviors in a NMDA receptor antagonist-reversible manner. These results suggest that ephrinB1 plays a crucial role in LPA-induced neuropathic pain.