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Published in: European Spine Journal 2/2008

01-02-2008 | Original Article

The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model

Authors: Miho Sekiguchi, Shin-ichi Konno, Shin-ichi Kikuchi

Published in: European Spine Journal | Issue 2/2008

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Abstract

Blood vessel clots are found around the nerve root in patients with lumbar disc herniation. Thrombosis formation in the experimental application of nucleus pulposus to the nerve root has been shown in histological studies. In addition, reduction of blood flow and nerve conduction velocity are induced by the application of nucleus pulposus, which mimics lumbar disc herniation. In patients with lumbar disc herniation, nerve root block, which is thought to increase nerve blood flow, improves radiculopathy. 5-HT2A receptor antagonists are used in chronic arterial occlusive diseases to improve blood flow and have been reported to work as well as nonsteroidal anti-inflammatory drugs in improving radiculopathy due to lumbar disc herniation in clinical studies. This study investigated the effects of a 5-HT2A receptor antagonist on blood vessel diameter and blood flow in a canine experimental model of lumbar disc herniation. A total of 13 dogs were used. The animals were divided into three experimental groups and surgery was performed 1 week before measurements. In the nucleus pulposus group (NP; n = 5), the nucleus pulposus was applied to the nerve roots from the ventral side. In the sham group (n = 5), nucleus pulposus was not applied. In the naïve group (n = 3), the animals did not undergo surgery. Measurements of vessel diameter and blood flow were done before and after administration of saline and drugs. The diameters and blood flow volume of the observed blood vessels were measured on video-recordings every 10 min for 65 min. In all groups, vessel diameter and blood flow did not change before or after administration of saline. In the NP and sham groups, vessel diameter and blood flow increased significantly after administration of 5-HTRA compared with the naïve group. 5-HTRA improved blood vessel diameter and blood flow in the nerve roots inflamed by the application of nucleus pulposus but not in the intact nerve roots. 5-HTRA might be a potential agent to improve blood flow in the nerve roots of patients with lumbar disc herniation.
Literature
1.
go back to reference Apperley E, Feniuk W, Humphrey PP et al (1980) Evidence for two types of excitatory receptor for 5-hydroxytryptamine in dog isolated vasculature. Br J Pharmacol 68:215–224PubMed Apperley E, Feniuk W, Humphrey PP et al (1980) Evidence for two types of excitatory receptor for 5-hydroxytryptamine in dog isolated vasculature. Br J Pharmacol 68:215–224PubMed
2.
go back to reference Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630PubMedCrossRef Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630PubMedCrossRef
3.
go back to reference Cohen ML, Fuller RW, Wiley KS (1982) Evidence for 5-HT2 receptor mediating contraction on vascular smooth muscle. J Pharmacol Exp Ther 218:421–425 Cohen ML, Fuller RW, Wiley KS (1982) Evidence for 5-HT2 receptor mediating contraction on vascular smooth muscle. J Pharmacol Exp Ther 218:421–425
4.
go back to reference Feniuk W, Humphrey PP, Perren MJ et al (1985) A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol 86:697–704PubMed Feniuk W, Humphrey PP, Perren MJ et al (1985) A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol 86:697–704PubMed
5.
go back to reference Habtemariam A, Gronblad M, Virri J et al (2002) Blood clots in vessels surrounding nymptomatic nerve roots in disc herniation patients: a pilot study. Eur Spine J 11:447–451PubMedCrossRef Habtemariam A, Gronblad M, Virri J et al (2002) Blood clots in vessels surrounding nymptomatic nerve roots in disc herniation patients: a pilot study. Eur Spine J 11:447–451PubMedCrossRef
6.
go back to reference Hara H, Osakabe M, Kitajima A (1991) MCI-9042, a new antiplatelate agent is a selective S2-serotonergic receptor antagonist. Thromb Haemost 65:415–420PubMed Hara H, Osakabe M, Kitajima A (1991) MCI-9042, a new antiplatelate agent is a selective S2-serotonergic receptor antagonist. Thromb Haemost 65:415–420PubMed
7.
go back to reference Hsahizume H, Kawakami M, Yoshida M et al (2007) Sarpogeralte hydrochloride, a 5-HT2A receptor antagonist, attenuated neurogenic pain induced by nucleus pulposus in rats. Spine 32:315–320CrossRef Hsahizume H, Kawakami M, Yoshida M et al (2007) Sarpogeralte hydrochloride, a 5-HT2A receptor antagonist, attenuated neurogenic pain induced by nucleus pulposus in rats. Spine 32:315–320CrossRef
8.
go back to reference Hotta N, Nakamura J, Sumita Y et al (1999) Effects of the 5-HT2A receptor antagonist Sarpogrelate in diabetic patients with complications: a pilot study. Clin Drug Investig 18:199–207CrossRef Hotta N, Nakamura J, Sumita Y et al (1999) Effects of the 5-HT2A receptor antagonist Sarpogrelate in diabetic patients with complications: a pilot study. Clin Drug Investig 18:199–207CrossRef
9.
go back to reference Igarashi T, Kikuchi S, Shubayev V, Myers RR (2000) 2000 Volvo award winner in basic science studies: exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine 25:2975–2980PubMedCrossRef Igarashi T, Kikuchi S, Shubayev V, Myers RR (2000) 2000 Volvo award winner in basic science studies: exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine 25:2975–2980PubMedCrossRef
10.
go back to reference Ishida T, Kawashima S, Hirata K et al (2001) Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries. Circulation 103:1289–1295PubMed Ishida T, Kawashima S, Hirata K et al (2001) Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries. Circulation 103:1289–1295PubMed
11.
go back to reference Kanayama M, Hashimoto T, Shigenobu K et al (2005) New treatment of lumbar disc herniation involving 5-hydroxytryptamine 2A receptor inhibitor: a randomized controlled trial. J Neurosurg Spine 2:441–446PubMedCrossRef Kanayama M, Hashimoto T, Shigenobu K et al (2005) New treatment of lumbar disc herniation involving 5-hydroxytryptamine 2A receptor inhibitor: a randomized controlled trial. J Neurosurg Spine 2:441–446PubMedCrossRef
12.
go back to reference Kato K, Kikuchi S, Konno S et al (2007) Participation of 5-hydroxytryptamine released to nerve root inflammation in lumbar disc herniation. ISSLS 34th meeting abstract, P115 Kato K, Kikuchi S, Konno S et al (2007) Participation of 5-hydroxytryptamine released to nerve root inflammation in lumbar disc herniation. ISSLS 34th meeting abstract, P115
13.
go back to reference Kayama S, Konno S, Kikuchi S et al (1996) Incision of the annulus fibrosus induces nerve root morphlogic, vascular, and functional changes. Spine 21:2539–2543PubMedCrossRef Kayama S, Konno S, Kikuchi S et al (1996) Incision of the annulus fibrosus induces nerve root morphlogic, vascular, and functional changes. Spine 21:2539–2543PubMedCrossRef
14.
go back to reference Leysen JE, DeChaffoy De Courcelles D, De Clerck F (1984) Serotonin-S2 receptor binding sites and functional correlates. Neuropharmacology 23:1493–1501PubMedCrossRef Leysen JE, DeChaffoy De Courcelles D, De Clerck F (1984) Serotonin-S2 receptor binding sites and functional correlates. Neuropharmacology 23:1493–1501PubMedCrossRef
15.
go back to reference Nishiyama T (2005) Effects of a 5-HT2A receptor antagnist, sarpogrelate on thermal or inflammatory pain. Eur J Pharmacol 516:18–22PubMedCrossRef Nishiyama T (2005) Effects of a 5-HT2A receptor antagnist, sarpogrelate on thermal or inflammatory pain. Eur J Pharmacol 516:18–22PubMedCrossRef
16.
go back to reference Nitanda A, Yasunami N, Tokumo K et al (2005) Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. Nuerochem Int 47:394–400CrossRef Nitanda A, Yasunami N, Tokumo K et al (2005) Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. Nuerochem Int 47:394–400CrossRef
17.
go back to reference Okamoto K, Imbe H, Morikawa Y et al (2002) 5-HT2A receptor sybtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats. Pain 99:133–143PubMedCrossRef Okamoto K, Imbe H, Morikawa Y et al (2002) 5-HT2A receptor sybtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats. Pain 99:133–143PubMedCrossRef
18.
go back to reference Olmarker K, Blomquist J, Rydevik B et al (1995) Inflammatogenic properties of nucleus pulposus. Spine 20:665–669PubMedCrossRef Olmarker K, Blomquist J, Rydevik B et al (1995) Inflammatogenic properties of nucleus pulposus. Spine 20:665–669PubMedCrossRef
19.
go back to reference Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induced neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432PubMed Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induced neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432PubMed
20.
go back to reference Olmarker K, Rydevik B (2001) Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity. Spine 26:863–869PubMedCrossRef Olmarker K, Rydevik B (2001) Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity. Spine 26:863–869PubMedCrossRef
21.
go back to reference Otani K, Arai I, Kikuchi S et al (1999) Nucleus pulposus-induced nerve root injury: relationship between blood flow and motor nerve conduction velocity. Neurosugery 45:614–619CrossRef Otani K, Arai I, Kikuchi S et al (1999) Nucleus pulposus-induced nerve root injury: relationship between blood flow and motor nerve conduction velocity. Neurosugery 45:614–619CrossRef
22.
go back to reference Otani K, Kikuchi S, Konno S (2001) Blood flow measurement on experimental chronic cauda equina compression in dogs: changes in blood flow at various conductions. J Spinal Disord 14:343–346PubMedCrossRef Otani K, Kikuchi S, Konno S (2001) Blood flow measurement on experimental chronic cauda equina compression in dogs: changes in blood flow at various conductions. J Spinal Disord 14:343–346PubMedCrossRef
23.
go back to reference Sasaki M, Obata H, Kawahara K et al (2006) Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats. Pain 122:130–136PubMedCrossRef Sasaki M, Obata H, Kawahara K et al (2006) Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats. Pain 122:130–136PubMedCrossRef
24.
go back to reference Sekiguchi M, Konno S, Kikuchi S (2004) Effects of 5-HT2A receptor antagonist on blood flow in chronically compressed nerve roots. J Peripher Nerv Syst 9:263–269PubMedCrossRef Sekiguchi M, Konno S, Kikuchi S (2004) Effects of 5-HT2A receptor antagonist on blood flow in chronically compressed nerve roots. J Peripher Nerv Syst 9:263–269PubMedCrossRef
25.
go back to reference Sekiguchi M, Konno S, Anzai H et al (2004) Nerve vasculature changes induced by serotonin under chronic cauda equina compression. Spine 27:1634–1639CrossRef Sekiguchi M, Konno S, Anzai H et al (2004) Nerve vasculature changes induced by serotonin under chronic cauda equina compression. Spine 27:1634–1639CrossRef
26.
go back to reference Sekiguchi M, Konno S, Kikuchi S (2006) Effects on improvement of blood flow in the chronically compressed cauda equina: comparison between a selective prostaglandin E receptor (EP4) agonist and a prostaglandin E1 derivate. Spine 31:869–872PubMedCrossRef Sekiguchi M, Konno S, Kikuchi S (2006) Effects on improvement of blood flow in the chronically compressed cauda equina: comparison between a selective prostaglandin E receptor (EP4) agonist and a prostaglandin E1 derivate. Spine 31:869–872PubMedCrossRef
27.
go back to reference Shimokawa H, Aarhus LL, Vanhoutte PM (1987) Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res 61:256–270PubMed Shimokawa H, Aarhus LL, Vanhoutte PM (1987) Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res 61:256–270PubMed
28.
29.
go back to reference Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 7:2897–2901PubMedCrossRef Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 7:2897–2901PubMedCrossRef
30.
go back to reference Xie QW, Cho HJ, Calaycay J et al (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228PubMedCrossRef Xie QW, Cho HJ, Calaycay J et al (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228PubMedCrossRef
31.
go back to reference Yabuki S, Kikuchi S, Olmarker K et al (1998) Acute effects of nucleus pulposus on blood flow and endoneurial fluid pressure in rat dorsal root ganglion. Spine 23:2517–2523PubMedCrossRef Yabuki S, Kikuchi S, Olmarker K et al (1998) Acute effects of nucleus pulposus on blood flow and endoneurial fluid pressure in rat dorsal root ganglion. Spine 23:2517–2523PubMedCrossRef
32.
go back to reference Yabiki S, Kikuchi S (1995) Nerve root infiltration and sympathetic block. An experimental study of intraradicular blood flow. Spine 20:901–906CrossRef Yabiki S, Kikuchi S (1995) Nerve root infiltration and sympathetic block. An experimental study of intraradicular blood flow. Spine 20:901–906CrossRef
Metadata
Title
The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model
Authors
Miho Sekiguchi
Shin-ichi Konno
Shin-ichi Kikuchi
Publication date
01-02-2008
Publisher
Springer-Verlag
Published in
European Spine Journal / Issue 2/2008
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-007-0534-4

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