Valproate reverses stress-induced somatic hyperalgesia and visceral hypersensitivity by up-regulating spinal 5-HT2C receptor expression in female rats

NEUROPHARMACOLOGY

卷:165

Article

Xu, Gang -Zhu^1,2  Xue, Yang¹  Wei, Si-Qi¹  Li, Jia-Heng¹  Traub, Richard J.³  Wang, Mao-De⁴  Cao, Dong-Yuan¹ 

[1] Xi An Jiao Tong Univ, Coll Stomatol, Res Ctr Stomatol, Key Lab Shaanxi Prov Craniofacial Precis Med Res, 98 West 5th Rd, Xian, Shaanxi, Peoples R China

[2] Xian Med Univ, Affiliated Hosp 1, Dept Neurosurg, Xian, Shaanxi, Peoples R China

[3] Univ Maryland, Sch Dent, UM Ctr Adv Chron Pain Res, Dept Neural & Pain Sci, 650 West Baltimore St, Baltimore, MD 21201 USA

[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurosurg, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China

关键词: Sodium valproate;    Serotonin;    Forced swim;    Fibromyalgia;    Visceromotor response;    Irritable bowel syndrome;   

DOI  :  10.1016/j.neuropharm.2019.107926

来源: Elsevier

【 摘 要 】

Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT2C receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT2C receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT2C receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT2C receptor antagonist RS-102221 (30 mu g/10 mu L) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT(2C )receptors in the spinal cord.

【 授权许可】

Free