Long-term administration of fluvoxamine attenuates neuropathic pain and involvement of spinal serotonin receptors in diabetic model rats

糖尿病モデルラットに対するフルボキサミンの長期投与は神経障害性疼痛を減弱させ、脊髄におけるセロトニン受容体の関与を変化させる

加藤 貴大

Diabetic neuropathic pain management is difficult even with non-steroidal anti-inflammatory drugs and narcotic analgesics such as morphine. Fluvoxamine, a class of selective serotonin reuptake inhibitors (SSRIs), is widely used to treat depression. Its analgesic effects are also documented for diabetic neuropathic pain, but they are limited because it is administered as a single-dose. In this study, we examined the time course of the antiallodynic effect of fluvoxamine in a rat model of diabetic neuropathic pain, which was induced by a single intraperitoneal administration of streptozotocin (75 mg/kg). In addition, the involvement of spinal serotonin (5-HT) receptors in long-term fluvoxamine treatment was studied by intrathecal administration of 5-HT receptor antagonists. In this study the development of mechanical hyperalgesia was assessed by measuring the hind paw withdrawal threshold using von Frey filaments. The results demonstrated that daily oral administration of fluvoxamine (10, 30, and 100 mg/kg) to diabetic rats from 3 to 8 weeks after streptozotocin administration resulted in a dose-dependent antiallodynic effect. The antiallodynic effect was sustained from 2 to 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine in the diabetic rats was attenuated by WAY-100635 (a 5-HT(1A) receptor antagonist) intrathecally administered 1 week after the onset of daily administration of fluvoxamine, whereas no significant attenuation was seen when the antagonist was administered 3 and 5 weeks after fluvoxamine administration. The antiallodynic effect of fluvoxamine was also attenuated by ketanserin (a 5-HT(2A/2C) receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist) intrathecally administered 1 and 3 weeks after the onset of daily fluvoxamine administration. However, no significant attenuation was observed when the antagonist was administered 5 weeks after fluvoxamine administration. This study demonstrated that daily oral administration of fluvoxamine can afford a sustained antiallodynic effect against streptozotocin-induced neuropathic pain. Furthermore, there appears to be a time-dependent relevance of different types of 5-HT receptors (5-HT(1A), 5-HT(2A/2C), and 5-HT3) to streptozotocin-induced diabetic neuropathic pain when treated with daily fluvoxamine.

Fluvoxamine

Diabetes

Serotonin receptor antagonist

Hyperalgesia

医学 [ 490 ]

英語

Copyright(c) by Author

[作成日] 2014-11-21

Kato Takahiro, Kajiyama Seiji, Hamada Hiroshi and Kawamoto Masashi; Long-term Administration of Fluvoxamine Attenuates Neuropathic Pain and Involvement of Spinal Serotonin Receptors in Diabetic Model Rats; Hiroshima Journal of Medical Sciences Vol.62 no.4 page.83-89 (2013-12) ～を参照している

広島大学