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

Aya Nakae, Kunihiro Nakai, Tatsuya Tanaka, Ko Hosokawa, Takashi Mashimo

Center for Medical Research and Education, Osaka University Graduate School of Medicine.
Department of Anesthesiology & Intensive Care, Osaka University Graduate School of Medicine.
Department of Plastic Surgery, Osaka University Graduate School of Medicine.

DOI: 10.4236/nm.2012.31011                

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 na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve 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.

Keywords

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

Conflicts of Interest

The authors declare no conflicts of interest.

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