Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia |
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| Authors: | Hitoshi Uchida Misaki Matsumoto Hiroshi Ueda |
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| Institution: | 1. Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, 201306, PR China;2. E-Institute of Shanghai Universities, Shanghai Ocean University, 999 Huchenghuan Road, 201306, Shanghai, PR China;1. Department of Microbiology, Osaka City Institute of Public Health and Environmental Sciences, 8-34 Tojo-cho, Tennoji-ku, Osaka 543-0026, Japan;2. Department of International Health, Institute of Tropical Medicine, Nagasaki University, Nagasaki, 1-12-4 Sakamoto, Nagasaki-shi, Nagasaki 852-8523, Japan;3. Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Orai-Kita, Izumisano-shi, Osaka 598-8531, Japan;1. Institute of Milk Hygiene, Milk Technology and Food Science, Department of Veterinary Public Health and Food Science, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria;2. Christian Doppler Laboratory for Molecular Food Analysis, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria |
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| Abstract: | 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. |
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