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Published on: May 12, 2018
Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal
1Department of Orthopaedic Surgery, School of Medicine, Chiba University, Japan. s.c.oh@pref-hosp.togane.chiba.jp
Abstract:
Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin. It has been suggested that members of this family control diverse processes in growth, development and the cell cycle.Here, we demonstrate that the DAN protein is produced in the small neurons of the dorsal root ganglion and is transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to the DAN protein suppressed inflammatory pain caused by the introduction of complete Freund's adjuvant or carrageenan into the rat hindpaw. The amount of mRNA for DAN in dorsal root ganglion neurons and of its expressed protein in the spinal dorsal horn were both increased in inflammatory models.Together, these data suggest that the DAN protein may be a novel neuromodulator in primary nociceptive nerve fibers.
Insights
Differential screening-selected gene aberrative in neuroblastoma (DAN) protein is found in pain-sensing neurons and may modulate inflammatory pain. Blocking DAN protein reduced pain responses in rat models, suggesting a novel therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Differential screening-selected gene aberrative in neuroblastoma (DAN) is a novel gene family member.
- DAN family members are implicated in growth, development, and cell cycle regulation.
- The role of DAN in the nervous system, particularly in pain, is largely unexplored.
Purpose of the Study:
- To investigate the presence and function of the DAN protein in the adult rat nervous system.
- To determine the potential role of DAN in inflammatory pain pathways.
- To explore DAN as a potential therapeutic target for pain management.
Main Methods:
- Immunohistochemistry to detect DAN protein localization in dorsal root ganglion (DRG) neurons and spinal cord.
- Intrathecal antibody injection to block DAN protein function in vivo.
- Assessment of inflammatory pain behavior in rat models (Complete Freund's Adjuvant and carrageenan).
- Quantitative analysis of DAN mRNA and protein levels in DRG and spinal cord under inflammatory conditions.
Main Results:
- DAN protein is expressed in small neurons of the dorsal root ganglion and transported to spinal dorsal horn nerve terminals.
- Intrathecal administration of anti-DAN antibody significantly suppressed inflammatory pain.
- Both DAN mRNA and protein levels were upregulated in DRG neurons and the spinal dorsal horn during inflammation.
Conclusions:
- The DAN protein is present in primary nociceptive nerve fibers.
- DAN plays a role in the modulation of inflammatory pain in rats.
- DAN represents a potential novel neuromodulator and therapeutic target for inflammatory pain.
