Role of peripheral and spinal 5-HT₃ receptors in development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia

详细信息	查看全文 | 推荐本文 |

• 作者：Mariana Bravo-Hern&#225 ; ndez^a ; ^b ; Claudia Cervantes-Dur&#225 ; n^a ; Jorge Baruch Pineda-Farias^a ; Paulino Barrag&#225 ; n-Iglesias^a ; Pedro Ló ; pez-S&#225 ; nchez^b ; Vinicio Granados-Soto^a ; ^{vgranados@prodigy.net.mx}
• 关键词：5-HT receptors ; Secondary hyperalgesia ; Secondary allodynia ; Chronic pain
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2012
• 期刊代码：219_00913057
• 类别：med
• 出版时间：April, 2012
• 卷：101
• 期：2
• 页码：246-257
• 文件大小：968 K

摘要

The role of peripheral and spinal 5-HT₃ receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In experiments where the test drug was anticipated to augment or antagonize the response, 0.5 or 1%formalin, respectively, was used for injection. Peripheral ipsilateral, but not contralateral, pre-treatment (鈭?#xA0;10 min) with serotonin (5-HT, 10-100 nmol/paw) and the selective 5-HT₃ receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG, 10-300 nmol/paw) increased 0.5%formalin-induced secondary allodynia and hyperalgesia in both paws. Moreover, spinal pre-treatment with m-CPBG (10-300 nmol/rat) increased 0.5%formalin-induced secondary hyperalgesia but not allodynia in both paws. Accordingly, peripheral ipsilateral (30-300 nmol/paw), but not contralateral (300 nmol/paw), and spinal (10-100 nmol) pre-treatment with the selective 5-HT₃ receptor antagonist ondansetron prevented 1%formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. The peripheral pronociceptive effects of 5-HT (100 nmol/paw) and m-CPBG (300 nmol/paw) as well as the spinal effect of m-CPBG (300 nmol/rat) were completely prevented by the peripheral (10 nmol/paw) and spinal (1 nmol/rat) injection, respectively, of ondansetron. At these doses, ondansetron did not modify per se formalin-induced nociceptive behaviors. Spinal (30-300 nmol/rat), but not peripheral (300 nmol/paw), post-treatment (on day 6) with ondansetron reversed established formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT₃ receptors participates in the development of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. In addition, our data suggest that spinal 5-HT₃ receptors play an important role during development and maintenance of these evoked long-term behaviors.