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http://dx.doi.org/10.3344/kjp.2014.27.3.219

Therapeutic Effect of Epidurally Administered Lipo-Prostaglandin E1 Agonist in a Rat Spinal Stenosis Model  

Park, Sang Hyun (Department of Anesthesiology and Pain Medicine, Jeju National University Hospital)
Lee, Pyung Bok (Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital)
Choe, Ghee Young (Department of Pathology, Seoul National University Bundang Hospital)
Moon, Jee Yeon (Department of Anesthesiology and Pain Medicine, Seoul National University Hospital)
Nahm, Francis Sahngun (Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital)
Kim, Yong Chul (Department of Anesthesiology and Pain Medicine, Seoul National University School of Medicine)
Publication Information
The Korean Journal of Pain / v.27, no.3, 2014 , pp. 219-228 More about this Journal
Abstract
Background: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, $0.15{\mu}g{\cdot}kg-1$ of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. Conclusions: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.
Keywords
epidural administration; hyperalgesia; spinal stenosis;
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1 Goupille P, Jayson MI, Valat JP, Freemont AJ. The role of inflammation in disk herniation-associated radiculopathy. Semin Arthritis Rheum 1998; 28: 60-71.   DOI
2 Thomas SA. Spinal stenosis: history and physical examination. Phys Med Rehabil Clin N Am 2003; 14: 29-39.   DOI
3 Swainston Harrison T, Plosker GL. Limaprost. Drugs 2007; 67: 109-18.   DOI   ScienceOn
4 Akuthota V, Lento P, Sowa G. Pathogenesis of lumbar spinal stenosis pain: why does an asymptomatic stenotic patient flare? Phys Med Rehabil Clin N Am 2003; 14: 17-28, v.   DOI
5 Mizushima Y, Yanagawa A, Hoshi K. Prostaglandin E1 is more effective, when incorporated in lipid microspheres, for treatment of peripheral vascular diseases in man. J Pharm Pharmacol 1983; 35: 666-7.   DOI
6 Murakami M, Takahashi K, Sekikawa T, Yasuhara K, Yamagata M, Moriya H. Effects of intravenous lipoprostaglandin E1 on neurogenic intermittent claudication. J Spinal Disord 1997; 10: 499-504.
7 Yone K, Sakou T, Kawauchi Y. The effect of Lipo prostaglandin E1 on cauda equina blood flow in patients with lumbar spinal canal stenosis: myeloscopic observation. Spinal Cord 1999; 37: 269-74.   DOI
8 Matsudaira K, Seichi A, Kunogi J, Yamazaki T, Kobayashi A, Anamizu Y, et al. The efficacy of prostaglandin E1 derivative in patients with lumbar spinal stenosis. Spine (Phila Pa 1976) 2009; 34: 115-20.   DOI   ScienceOn
9 Mizushima Y. Lipo-prostaglandin preparations. Prostaglandins Leukot Essent Fatty Acids 1991; 42: 1-6.   DOI   ScienceOn
10 Kawamura T, Akira T, Watanabe M, Kagitani Y. Prostaglandin E1 prevents apoptotic cell death in superficial dorsal horn of rat spinal cord. Neuropharmacology 1997; 36: 1023-30.   DOI
11 Kawamura T, Horie S, Maruyama T, Akira T, Imagawa T, Nakamura N. Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation. J Neurochem 1999; 72: 1907-14.
12 Gensch C, Clever Y, Werner C, Hanhoun M, Bohm M, Laufs U. Regulation of endothelial progenitor cells by prostaglandin E1 via inhibition of apoptosis. J Mol Cell Cardiol 2007; 42: 670-7.   DOI   ScienceOn
13 Lim YJ, Sim WS, Kim YC, Lee SC, Choi YL. The neurotoxicity of epidural hyaluronic acid in rabbits: a light and electron microscopic examination. Anesth Analg 2003; 97: 1716-20.   DOI   ScienceOn
14 Kawakami M, Weinstein JN, Spratt KF, Chatani K, Traub RJ, Meller ST, et al. Experimental lumbar radiculopathy. Immunohistochemical and quantitative demonstrations of pain induced by lumbar nerve root irritation of the rat. Spine (Phila Pa 1976) 1994; 19: 1780-94.   DOI   ScienceOn
15 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63.   DOI   ScienceOn
16 Dixon WJ, Massey FJ. Introduction to statistical analysis. 3rd ed. New York (NY), McGraw-Hill. 1969.
17 Safonova GD, Kovalenko AP. Morphofunctional characteristics of neurons in the spinal ganglia of the dog in the post-distraction period. Neurosci Behav Physiol 2006; 36: 491-4.   DOI
18 Rydevik BL, Myers RR, Powell HC. Pressure increase in the dorsal root ganglion following mechanical compression. Closed compartment syndrome in nerve roots. Spine (Phila Pa 1976) 1989; 14: 574-6.   DOI   ScienceOn
19 Andreollo NA, Santos EF, Araújo MR, Lopes LR. Rat's age versus human's age: what is the relationship? Arq Bras Cir Dig 2012; 25: 49-51.   DOI
20 Nakai K, Takenobu Y, Takimizu H, Akimaru S, Ito H, Maegawa H, et al. Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model. Prostaglandins Leukot Essent Fatty Acids 2003; 69: 269-73.   DOI
21 Shirasaka M, Takayama B, Sekiguchi M, Konno S, Kikuchi S. Vasodilative effects of prostaglandin E1 derivate on arteries of nerve roots in a canine model of a chronically compressed cauda equina. BMC Musculoskelet Disord 2008; 9: 41.   DOI
22 Yoon HK, Lee PB, Han JS, Park SH, Lee SY, Kim YH, et al. The effect of intravenous lipo-prostaglandin E1 injectioin in a rat foraminal stenosis model. Korean J Pain 2007; 20: 15-20.   DOI
23 Song XJ, Hu SJ, Greenquist KW, Zhang JM, LaMotte RH. Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. J Neurophysiol 1999; 82: 3347-58.
24 Hirano A. Neurons and astrocytes. In: Textbook of neuropathology. 3rd ed. Edited by Davis RL, Robertson DM. Baltimore (MA), Williams & Wilkins. 1997, pp 5-7.
25 Levine S, Saltzman A, Kumar AR. A method for peripheral chromatolysis in neurons of trigeminal and dorsal root ganglia, produced in rats by lithium. J Neurosci Methods 2004; 132: 1-7.   DOI
26 Naruo S, Okajima K, Taoka Y, Uchiba M, Nakamura T, Okabe H, et al. Prostaglandin E1 reduces compression traumainduced spinal cord injury in rats mainly by inhibiting neutrophil activation. J Neurotrauma 2003; 20: 221-8.   DOI
27 Manchikanti L, Boswell MV, Datta S, Fellows B, Abdi S, Singh V, et al. Comprehensive review of therapeutic interventions in managing chronic spinal pain. Pain Physician 2009; 12: E123-98.
28 Cavanaugh JM, Ozaktay AC, Yamashita T, Avramov A, Getchell TV, King AI. Mechanisms of low back pain: a neurophysiologic and neuroanatomic study. Clin Orthop Relat Res 1997; (335): 166-80.
29 Kim YC, Lim YJ, Lee SC. Spreading pattern of epidurally administered contrast medium in rabbits. Acta Anaesthesiol Scand 1998; 42: 1092-5.   DOI   ScienceOn
30 Hu SJ, Xing JL. An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 1998; 77: 15-23.   DOI   ScienceOn
31 Sekikawa T, Murakami M, Takahashi K, Yamagata M, Yasuhara K, Nemoto T, et al. Effects of lipo-prostaglandin E1 on blood flow and oxygen pressure in lumbo-sacral nerve roots. J Orthop Sci 1997; 2: 289-94.   DOI   ScienceOn
32 Salafia CM, Weigl C, Silberman L. The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. Obstet Gynecol 1989; 73: 383-9.
33 Epstein NE. The risks of epidural and transforaminal steroid injections in the Spine: commentary and a comprehensive review of the literature. Surg Neurol Int 2013; 4: S74-93.