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

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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.

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Reference

  1. 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 68:215–224

    PubMed  CAS  Google Scholar 

  2. Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630

    Article  PubMed  CAS  Google Scholar 

  3. 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

    Google Scholar 

  4. 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 86:697–704

    PubMed  CAS  Google Scholar 

  5. 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 11:447–451

    Article  PubMed  Google Scholar 

  6. Hara H, Osakabe M, Kitajima A (1991) MCI-9042, a new antiplatelate agent is a selective S2-serotonergic receptor antagonist. Thromb Haemost 65:415–420

    PubMed  CAS  Google Scholar 

  7. 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 32:315–320

    Article  Google Scholar 

  8. 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 18:199–207

    Article  CAS  Google Scholar 

  9. 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 25:2975–2980

    Article  PubMed  CAS  Google Scholar 

  10. Ishida T, Kawashima S, Hirata K et al (2001) Serotonin-induced hypercontraction through 5-hydroxytryptamine 1B receptors in atherosclerotic rabbit coronary arteries. Circulation 103:1289–1295

    PubMed  CAS  Google Scholar 

  11. 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 2:441–446

    Article  PubMed  Google Scholar 

  12. 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. Kayama S, Konno S, Kikuchi S et al (1996) Incision of the annulus fibrosus induces nerve root morphlogic, vascular, and functional changes. Spine 21:2539–2543

    Article  PubMed  CAS  Google Scholar 

  14. Leysen JE, DeChaffoy De Courcelles D, De Clerck F (1984) Serotonin-S2 receptor binding sites and functional correlates. Neuropharmacology 23:1493–1501

    Article  PubMed  CAS  Google Scholar 

  15. Nishiyama T (2005) Effects of a 5-HT2A receptor antagnist, sarpogrelate on thermal or inflammatory pain. Eur J Pharmacol 516:18–22

    Article  PubMed  CAS  Google Scholar 

  16. 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 47:394–400

    Article  CAS  Google Scholar 

  17. 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 99:133–143

    Article  PubMed  CAS  Google Scholar 

  18. Olmarker K, Blomquist J, Rydevik B et al (1995) Inflammatogenic properties of nucleus pulposus. Spine 20:665–669

    Article  PubMed  CAS  Google Scholar 

  19. Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induced neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432

    PubMed  CAS  Google Scholar 

  20. 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 26:863–869

    Article  PubMed  CAS  Google Scholar 

  21. 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 45:614–619

    Article  CAS  Google Scholar 

  22. 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 14:343–346

    Article  PubMed  CAS  Google Scholar 

  23. 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 122:130–136

    Article  PubMed  CAS  Google Scholar 

  24. 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 9:263–269

    Article  PubMed  CAS  Google Scholar 

  25. Sekiguchi M, Konno S, Anzai H et al (2004) Nerve vasculature changes induced by serotonin under chronic cauda equina compression. Spine 27:1634–1639

    Article  Google Scholar 

  26. 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 31:869–872

    Article  PubMed  Google Scholar 

  27. 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 61:256–270

    PubMed  CAS  Google Scholar 

  28. Vanhoutte PM (1990) Serotonergic antagonists and vascular disease. Cardiovasc Drugs Ther 4:7–12

    Article  PubMed  Google Scholar 

  29. Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 7:2897–2901

    Article  PubMed  CAS  Google Scholar 

  30. Xie QW, Cho HJ, Calaycay J et al (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228

    Article  PubMed  CAS  Google Scholar 

  31. 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 23:2517–2523

    Article  PubMed  CAS  Google Scholar 

  32. Yabiki S, Kikuchi S (1995) Nerve root infiltration and sympathetic block. An experimental study of intraradicular blood flow. Spine 20:901–906

    Article  Google Scholar 

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Correspondence to Miho Sekiguchi.

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Sekiguchi, M., Konno, Si. & Kikuchi, Si. The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model. Eur Spine J 17, 307–313 (2008). https://doi.org/10.1007/s00586-007-0534-4

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  • DOI: https://doi.org/10.1007/s00586-007-0534-4

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