title: Effects of 5-HT2A receptor antagonist on blood flow in chronically compressed nerve roots.
abstract: Neurogenic intermittent claudication (NIC) can be caused by compression of the cauda equina by spinal stenosis and is a major clinical problem. A reduction of blood flow is an important mechanism for inducing NIC and may be caused by a vasoconstrictive effect mediated by the serotonin 5-HT2A receptor in chronic cauda equina compression lesions. This study assessed the effects of the 5-HT2A receptor antagonist on nerve vasculature in chronically compressed nerve roots. A plastic balloon was placed under the lamina of L7 and inflated to 10 mmHg and left for 1 week in several cauda equina compression models. All experimental animals received an acute administration of serotonin. One group received sarpogrelate hydrochloride (5-HT2A receptor antagonist: 5-HTRA) before administration of serotonin, and another group was administered 5-HTRA after administration of serotonin. Diameters and blood flow in the vasculature of S2 or S3 nerve roots were measured after injection of serotonin. In animals without compression of the cauda equina (sham), blood vessels contracted and the blood flow was reduced after administration of serotonin. In sham and compression animals receiving both serotonin and 5-HTRA, blood vessel diameter was not reduced and was significantly larger than that in the compression group receiving only serotonin (p<0.05). Likewise, the blood flow was not reduced in sham and compression animals receiving serotonin and 5-HTRA and was significantly greater in the compression group treated only with serotonin. 5-HTRA inhibited vasoconstriction and the reduction of blood flow in chronically compressed nerve roots challenged with serotonin. This fact suggests that 5-HTRA might be effective at improving blood flow in chronically compressed nerve roots in patients with spinal canal stenosis and changes in circulation levels of serotonin.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan. miho-s@fmu.ac.jp
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Konno
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D004285:Dogs; D011843:Radiculopathy / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013126:Spinal Nerve Roots / Q000098:blood supply* / Q000187:drug effects; D013386:Succinates / Q000494:pharmacology*
chemical_list: D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin