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Serotonin 2C receptor alternative splicing in a spinal cord injury model
Aya Nakae1, Kunihiro Nakai, Tatsuya Tanaka
1Osaka University Graduate School of Medicine, Department of Anesthesiology & Intensive Care, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. anakae@anes.med.osaka-u.ac.jp
Neuroscience Letters
|November 6, 2012
Summary
Spinal cord injury in rats reduced pain thresholds and altered serotonin 2C receptor (5HTR2C) expression and splicing. This suggests spinal injury causes neuropathic pain via serotonergic dysfunction involving 5HTR2C RNA editing and alternative splicing.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Spinal cord injury (SCI) leads to motor deficits and chronic pain.
- The serotonin pathway, particularly the serotonin 2C receptor (5HTR2C), plays a role in motor function and pain inhibition after SCI.
- 5HTR2C regulation involves receptor levels, RNA editing, and alternative splicing.
Purpose of the Study:
- To investigate the link between pain threshold and 5HTR2C alternative splicing following spinal contusion injury in a rat model.
- To analyze changes in 5HTR2C RNA levels and splicing patterns at different spinal cord locations post-injury.
Main Methods:
- Rats underwent spinal contusion injury or sham surgery.
- Pain threshold was measured using von Frey filaments.
- Real-time PCR was employed to quantify 5HTR2C RNA levels and assess alternative splicing (exon Vb-skipped variants) in rostral, injury-core, and caudal spinal cord sections.
Main Results:
- Injured rats exhibited significantly reduced pain thresholds compared to controls.
- Total 5HTR2C levels were decreased in injured rats at all measured spinal cord locations.
- The ratio of nonfunctional exon Vb-skipped 5HTR2C mRNA to total 5HTR2C increased significantly in injured rats, particularly at the injury site and caudal regions.
Conclusions:
- Spinal contusion injury induces neuropathic pain associated with serotonergic dysfunction.
- This dysfunction is mediated by reduced 5HTR2C mRNA expression and altered alternative splicing.
- Considering 5HTR2C splice variants is crucial for understanding its role in SCI-induced pain.
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