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Serotonin 2C Receptor Alternative Splicing in a Rat Model of Orofacial Neuropathic Pain

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Author(s): Aya Nakae | Kunihiro Nakai | Tatsuya Tanaka | Ko Hosokawa | Takashi Mashimo

Journal: Neuroscience & Medicine
ISSN 2158-2912

Volume: 03;
Issue: 01;
Start page: 69;
Date: 2012;
Original page

Keywords: Orofacial Neuropathic Pain | Prader-Willi Syndrome | Serotonin 2C Receptor | Alternative Splicing | SnoRNA | RBII-52 | RNA Editing | Spinal Cord

ABSTRACT
Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA; the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or naïve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or naïve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.
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