The role of RNA editing of the serotonin 2C receptor in a rat model of oro-facial neuropathic pain.
We examined whether infraorbital nerve injury affected the RNA editing efficiency of the serotonin (5HT) 2C receptor in the cervical spinal cord, in association with increased pain thresholds, and whether a 5HT reuptake inhibitor (fluvoxamine; Depromel, Meiji Seika, Tokyo, Japan) altered this editing. Accordingly, we injured rats with an infraorbital nerve loose ligation and examined the pain thresholds, mRNA and mRNA editing of the 5HT2C receptor. We evaluated changes in mRNA editing and 5HT2C mRNA expression using cloning along with sequence analysis and quantitative reverse transcription-polymerase chain reaction to compare samples taken at post-injury day 28 from spinal cord sites, including the trigeminal nucleus caudalis, in naive, sham and injured rats (groups of each type had also received fluvoxamine). 5HT2C receptor expression was maintained post-injury. The RNA editing efficiency was statistically significantly lower at molecular sites A and B in ipsilateral spinal cord samples from injured rats than in bilateral samples from naive and sham rats, and in contralateral samples from injured rats. After injury, the proportional presence of two receptor isoforms changed, i.e. statistically significantly less VNV and significantly more INV and ISV. The proportions reverted after fluvoxamine administration. The post-injury change might be evidence of a functional adaptation mechanism that increases the expression of 5HT2C mRNA isoforms that encode receptors that are more sensitive to 5HT. This would activate the brainstem-spinal descending 5HT systems and, in effect, suppress nociceptive signals from primary afferent neurons to the spinal trigeminal nucleus caudalis.
Nakae
Aya
A
Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, Japan. anakae@anes.med.osaka-u.ac.jp
Nakai
Kunihiro
K
Tanaka
Tatsuya
T
Hagihira
Saotoshi
S
Shibata
Masahiko
M
Ueda
Koichi
K
Masimo
Takashi
T
D000818:Animals; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D005157:Facial Pain / Q000235:genetics*; D016666:Fluvoxamine / Q000494:pharmacology; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D017393:RNA Editing / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000503:physiopathology
D016666:Fluvoxamine; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D017367:Selective Serotonin Reuptake Inhibitors