| 研究生: |
陳佩鈺 Chen, Pei-yu |
|---|---|
| 論文名稱: |
椎板切除術後瘢痕組織與神經根之形態學研究 Morphological study of the neuropathic pain following lumbar laminectomy |
| 指導教授: |
周一鳴
Jou, I-Ming 曾啟育 Tseng, Chi-Yu 李世雄 Lee, shih-shiung |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 細胞生物與解剖學研究所 Institute of Cell Biology and Anatomy |
| 論文出版年: | 2007 |
| 畢業學年度: | 95 |
| 語文別: | 中文 |
| 論文頁數: | 71 |
| 中文關鍵詞: | 椎板切除術 、脊椎術後症候群 、脊椎術後瘢痕組織 |
| 外文關鍵詞: | epidural fibrosis, failed back surgery syndrome (FBSS), laminectomy |
| 相關次數: | 點閱:73 下載:1 |
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椎板切除術 (laminectomy) 是目前最常用來緩解神經根壓迫、坐骨神經痛、下肢疼痛以及下背痛的手術。然而在手術後長期追蹤下,發現竟然有高達40%的病人不滿意手術結果,顯然就長期而言,脊椎手術之結果仍然未臻理想。而無論何種原因引起背痛,經手術後症狀沒有改善,卻依然有持續背痛等症狀,在臨床上統稱為脊椎術後症候群 (failed back surgery syndrome; FBSS)。造成脊椎術後症候群的原因有很多,且牽涉的層面相當廣泛,但是在眾多原因之中,術後瘢痕組織 (epidural fibrosis) 的形成可說是一個明顯且重要的因素;據臨床報告指出,約有24-60%脊椎術後症候群的患者是由瘢痕組織所引起。有學者認為,瘢痕組織之所以會造成術後的併發症狀,是因為瘢痕組織對脊柱內神經組織產生沾粘、壓迫和撕扯的作用;反觀使用MRI深入研究後,卻有學者提出不同的意見;直至目前為止,雖然大多數的學者主張脊椎術後瘢痕組織確實會引起脊椎術後疼痛與坐骨神經痛,但是,究竟它是如何引起術後疼痛其確實的機轉仍然未有定論。在此之前,針對纖維組織的大小及延伸已有許多組織學上的探討,但是針對鄰近纖維化的神經纖維,如馬尾束神經根、背根神經節或纖維組織,其細胞構造卻鮮少深入研究。而於我們實驗室前一階段研究發現,瘢痕組織所沾粘的馬尾區域之神經根在光學顯微鏡觀察下似乎有病理上的變化,因此,本實驗的第一個目的,就是要更進一步使用電子顯微鏡去探討這些神經根之超微結構。除此之外,我們根據多數學者的研究結果,提出實驗假說,認為脊椎術後瘢痕組織的生長與脊椎術後症候群應有相當程度的關聯;術後瘢痕組織內可能有神經異常增生,並且這些增生的神經是與疼痛有關之神經纖維。我們使用一般研究脊椎術後瘢痕組織的動物實驗模式,利用免疫染色、光學顯微鏡及電子顯微鏡,進一步探討脊椎術後瘢痕組織與脊椎術後症候群在病態生理學上的關連性。根據實驗結果發現,脊椎術後瘢痕組織所沾粘區域之神經纖維發生髓鞘與軸突的病變,而此病變絕大部分都發生在大型神經纖維,並且也觀察到發炎細胞出現在神經根當中。而針對瘢痕組織進一步觀察發現,確實有神經異常增生至術後瘢痕組織當中,而這些增生的神經,包括痛覺神經纖維以及交感神經纖維。總結實驗結果,我們推論,因術後瘢痕組織所引發的脊椎術後症候群之症狀,不僅是由瘢痕組織壓迫神經根所造成,術後神經根的病變以及瘢痕組織中異常增生的神經,都可能是造成脊椎術後症候群的原因之一。
Background data: Failed back surgery syndrome (FBSS) is a frustrated complication for the patients and spinal surgeons. Among the various etiologies, postlaminectomy peridural fibrosis is thought to be an important cause of FBSS. The relevance between the fibrotic scar and the postoperative pain following lumbar laminectomy is, however, still unclear. Objective: To assess if the postlaminectomy induced epidural fibrosis would be the cause of FBSS. Study design: The morphological changes of the neural tissues, including the epidural fibrotic scar, cauda equina, and the dorsal root ganglion, after laminectomy were assayed. Method: The neural tissues were harvested from rats at postlaminectomy (L5) 1- and 3- month later and analyzed by electron microscopy and immunohistochemistry. Results: Degenerative changes with dysmyelination and progressive axonopathy which occurred in the intradural nerve roots adjacent to the postlaminectomy epidural fibrosis. Besides, many inflammatory cells infiltration were observed. In the epidural fibrotic tissue, the appearance of new in-growth fibers, which showed immunoactive to protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and calcitonin gene-related peptide (CGRP), were suggestive to possess both pain and sympathetic nerve components. In the dorsal root ganglion, there were increasing lipofuscin granules accumulated in the cytoplasm of sensory neuronal soma. Conclusions: These findings indicate the epidural fibrosis play a certain role in the FBSS.
Abitbol JJ, Lincoln TL, Lind BI, Amiel D, Akeson WH, Garfin SR. Preventing postlaminectomy adhesion. A new experimental model. Spine 1994;19(16):1809-1814.
Ahmed M, Bjurholm A, Kreicbergs A, Schultzberg M. Neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide-immunoreactive nerve fibers in the vertebral bodies, discs, dura mater, and spinal ligaments of the rat lumbar spine. Spine 1993;18(2):268-273.
Ahn UM, Ahn NU, Buchowski JM, Garrett ES, Sieber AN, Kostuik JP. Cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes. Spine 2000;25(12):1515-1522.
Allan DB, Waddell G. An historical perspective on low back pain and disability. Acta Orthop Scand Suppl 1989;234:1-23.
Anand P. Neurotrophic factors and their receptors in human sensory neuropathies. Progress in brain research 2004;146:477-492.
Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354(9178):581-585.
Annertz M, Jonsson B, Stromqvist B, Holtas S. No relationship between epidural fibrosis and sciatica in the lumbar postdiscectomy syndrome. A study with contrast-enhanced magnetic resonance imaging in symptomatic and asymptomatic patients. Spine 1995;20(4):449-453.
Ashton IK, Roberts S, Jaffray DC, Polak JM, Eisenstein SM. Neuropeptides in the human intervertebral disc. J Orthop Res 1994a;12(2):186-192.
Ashton IK, Walsh DA, Polak JM, Eisenstein SM. Substance P in intervertebral discs. Binding sites on vascular endothelium of the human annulus fibrosus. Acta orthopaedica Scandinavica 1994b;65(6):635-639.
Baik E, Chung JM, Chung K. Peripheral norepinephrine exacerbates neuritis-induced hyperalgesia. J Pain 2003;4(4):212-221.
Banik RK, Sato J, Yajima H, Mizumura K. Differences between the Lewis and Sprague-Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors. Neuroscience letters 2001;299(1-2):21-24.
Bobechko WP, Hirsch C. Auto-Immune Response to Nucleus Pulposus in the Rabbit. J Bone Joint Surg Br 1965;47:574-580.
Bogduk N. The innervation of the lumbar spine. Spine 1983;8(3):286-293.
Bressler HB, Keyes WJ, Rochon PA, Badley E. The prevalence of low back pain in the elderly. A systematic review of the literature. Spine 1999;24(17):1813-1819.
Bundschuh CV, Modic MT, Ross JS, Masaryk TJ, Bohlman H. Epidural fibrosis and recurrent disk herniation in the lumbar spine: MR imaging assessment. Ajr 1988;150(4):923-932.
Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff KB. Causes of failure of surgery on the lumbar spine. Clinical orthopaedics and related research 1981(157):191-199.
Cauchoix J, Ficat C, Girard B. Repeat surgery after disc excision. Spine 1978;3(3):256-259.
Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 1994;59(3):369-376.
Clatworthy AL, Illich PA, Castro GA, Walters ET. Role of peri-axonal inflammation in the development of thermal hyperalgesia and guarding behavior in a rat model of neuropathic pain. Neuroscience letters 1995;184(1):5-8.
Demeure CE, Brahimi K, Hacini F, Marchand F, Peronet R, Huerre M, St-Mezard P, Nicolas JF, Brey P, Delespesse G, Mecheri S. Anopheles mosquito bites activate cutaneous mast cells leading to a local inflammatory response and lymph node hyperplasia. J Immunol 2005;174(7):3932-3940.
Deyo RA. Early diagnostic evaluation of low back pain. J Gen Intern Med 1986;1(5):328-338.
Deyo RA. The role of the primary care physician in reducing work absenteeism and costs due to back pain. Occupational medicine (Philadelphia, Pa 1988;3(1):17-30.
Diwan AD, Parvartaneni H, Cammisa F. Failed degenerative lumbar spine surgery. The Orthopedic clinics of North America 2003;34(2):309-324.
Djukic S, Lang P, Morris J, Hoaglund F, Genant HK. The postoperative spine. Magnetic resonance imaging. The Orthopedic clinics of North America 1990;21(3):603-624.
Ebeling U, Reichenberg W, Reulen HJ. Results of microsurgical lumbar discectomy. Review on 485 patients. Acta neurochirurgica 1986;81(1-2):45-52.
Faurschou M, Borregaard N. Neutrophil granules and secretory vesicles in inflammation. Microbes and infection / Institut Pasteur 2003;5(14):1317-1327.
Finnegan WJ, Fenlin JM, Marvel JP, Nardini RJ, Rothman RH. Results of surgical intervention in the symptomatic multiply-operated back patient. Analysis of sixty-seven cases followed for three to seven years. The Journal of bone and joint surgery 1979;61(7):1077-1082.
Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O'Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 1997;350(9072):178-181.
Fritsch EW, Heisel J, Rupp S. The failed back surgery syndrome: reasons, intraoperative findings, and long-term results: a report of 182 operative treatments. Spine 1996;21(5):626-633.
Gerszten PC, Moossy JJ, Bahri S, Kalend A, Martinez AJ. Inhibition of peridural fibrosis after laminectomy using low-dose external beam radiation in a rat model. Neurosurgery 1999;44(3):597-602; discussion 602-593.
Habler H, Eschenfelder S, Liu XG, Janig W. Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow. Pain 2000;87(3):335-345.
Hazard RG. Failed back surgery syndrome: surgical and nonsurgical approaches. Clinical orthopaedics and related research 2006;443:228-232.
He Y, Revel M, Loty B. A quantitative model of post-laminectomy scar formation. Effects of a nonsteroidal anti-inflammatory drug. Spine 1995;20(5):557-563; discussion 579-580.
Hinton JL, Jr., Warejcka DJ, Mei Y, McLendon RE, Laurencin C, Lucas PA, Robinson JS, Jr. Inhibition of epidural scar formation after lumbar laminectomy in the rat. Spine 1995;20(5):564-570; discussion 579-580.
Hsieh ST, Lin WM. Modulation of keratinocyte proliferation by skin innervation. The Journal of investigative dermatology 1999;113(4):579-586.
Imai S, Hukuda S, Maeda T. Dually innervating nociceptive networks in the rat lumbar posterior longitudinal ligaments. Spine 1995;20(19):2086-2092.
John A. Kiernan. Barr’s the human nervous system. Lippincott-Raven. Philadelphia, PA. USA. 1998; 346-349.
Jou IM, Tai TW, Tsai CL, Tsai TM, Yung WS, Jung YC. Spinal Somatosensory Evoked Potential to Evaluate Neurophysiological Changes Associated with
Post-laminotomy Fibrosis: An Experimental Study. Spine 2007.
Kim SH, Na HS, Sheen K, Chung JM. Effects of sympathectomy on a rat model of peripheral neuropathy. Pain 1993;55(1):85-92.
LaRocca H, Macnab I. The laminectomy membrane. Studies in its evolution, characteristics, effects and prophylaxis in dogs. J Bone Joint Surg Br 1974;56B(3):545-550.
Lavand'homme P, Pan HL, Eisenach JC. Intrathecal neostigmine, but not sympathectomy, relieves mechanical allodynia in a rat model of neuropathic pain. Anesthesiology 1998;89(2):493-499.
Lee CK, Alexander H. Prevention of postlaminectomy scar formation. Spine 1984;9(3):305-312.
Lee DH, Iyengar S, Lodge D. The role of uninjured nerve in spinal nerve ligated rats points to an improved animal model of neuropathic pain. European journal of pain (London, England) 2003;7(5):473-479.
Lee DH, Katner J, Iyengar S, Lodge D. The effect of lumbar sympathectomy on increased tactile sensitivity in spinal nerve ligated rats. Neuroscience letters 2001;298(2):99-102.
Lee DH, Liu X, Kim HT, Chung K, Chung JM. Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. Journal of neurophysiology 1999;81(5):2226-2233.
Lee JY, Stenzel W, Impekoven P, Theisohn M, Stutzer H, Lohr M, Reithmeier T, Ernestus RI, Ebel H, Klug N. The effect of mitomycin C in reducing epidural fibrosis after lumbar laminectomy in rats. J Neurosurg Spine 2006a;5(1):53-60.
Lee JY, Stenzel W, Lohr M, Stutzer H, Ernestus RI, Klug N. The role of mitomycin C in reducing recurrence of epidural fibrosis after repeated operation in a laminectomy model in rats. J Neurosurg Spine 2006b;4(4):329-333.
Levine JD, Gooding J, Donatoni P, Borden L, Goetzl EJ. The role of the polymorphonuclear leukocyte in hyperalgesia. J Neurosci 1985;5(11):3025-3029.
Lin WM, Hsieh ST, Huang IT, Griffin JW, Chen WP. Ultrastructural localization and regulation of protein gene product 9.5. Neuroreport 1997;8(14):2999-3004.
Long DM. Failed back surgery syndrome. Neurosurgery clinics of North America 1991;2(4):899-919.
Malter AD, McNeney B, Loeser JD, Deyo RA. 5-year reoperation rates after different types of lumbar spine surgery. Spine 1998;23(7):814-820.
Manchikanti L, Pampati V, Fellows B, Rivera J, Beyer CD, Damron KS. Role of one day epidural adhesiolysis in management of chronic low back pain: a randomized clinical trial. Pain physician 2001;4(2):153-166.
Manning, D. The role of neuroimmune activation in chronic neuropathic pain and new targets for therapeutic intervention. In Emerging Strategies for the Treatment of Neuropathic. In: Basbaum AI, Campbell JN, Dray A, Dubner R, Dworkin RH, Sang CN. , editors. Pain. Seattle, WA: IASP Press; 2006. pp. 161–192.
Mearow KM, Kril Y, Diamond J. Increased NGF mRNA expression in denervated rat skin. Neuroreport 1993;4(4):351-354.
Merrild U, Sogaard I. Sciatica caused by perifibrosis of the sciatic nerve. J Bone Joint Surg Br 1986;68(5):706.
Mikawa Y, Hamagami H, Shikata J, Higashi S, Yamamuro T, Hyon SH, Ikada Y. An experimental study on prevention of postlaminectomy scar formation by the use of new materials. Spine 1986;11(8):843-846.
Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain research reviews 2006;51(2):240-264.
Moalem G, Xu K, Yu L. T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 2004;129(3):767-777.
Moon DE, Lee DH, Han HC, Xie J, Coggeshall RE, Chung JM. Adrenergic sensitivity of the sensory receptors modulating mechanical allodynia in a rat neuropathic pain model. Pain 1999;80(3):589-595.
North RB, Campbell JN, James CS, Conover-Walker MK, Wang H, Piantadosi S, Rybock JD, Long DM. Failed back surgery syndrome: 5-year follow-up in 102 patients undergoing repeated operation. Neurosurgery 1991;28(5):685-690; discussion 690-681.
Nygaard OP, Kloster R, Dullerud R, Jacobsen EA, Mellgren SI. No association between peridural scar and outcome after lumbar microdiscectomy. Acta neurochirurgica 1997;139(12):1095-1100.
Olmarker K, Nordborg C, Larsson K, Rydevik B. Ultrastructural changes in spinal nerve roots induced by autologous nucleus pulposus. Spine 1996;21(4):411-414.
Olmarker K, Rydevik B, Nordborg C. Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 1993;18(11):1425-1432.
Pappas CT, Harrington T, Sonntag VK. Outcome analysis in 654 surgically treated lumbar disc herniations. Neurosurgery 1992;30(6):862-866.
Park SK, Chung K, Chung JM. Effects of purinergic and adrenergic antagonists in a rat model of painful peripheral neuropathy. Pain 2000;87(2):171-179.
Perkins NM, Tracey DJ. Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 2000;101(3):745-757.
Perry VH, Brown MC, Gordon S. The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. The Journal of experimental medicine 1987;165(4):1218-1223.
Pheasant H. Sources of failure in laminectomies. The Orthopedic clinics of North America 1975;6(1):319-329.
Ramer MS, Bisby MA. Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a chronic constriction injury. Pain 1997;70(2-3):237-244.
Ren Y, Zou X, Fang L, Lin Q. Sympathetic modulation of activity in Adelta- and C-primary nociceptive afferents after intradermal injection of capsaicin in rats. Journal of neurophysiology 2005;93(1):365-377.
Ringkamp M, Eschenfelder S, Grethel EJ, Habler HJ, Meyer RA, Janig W, Raja SN. Lumbar sympathectomy failed to reverse mechanical allodynia- and hyperalgesia-like behavior in rats with L5 spinal nerve injury. Pain 1999;79(2-3):143-153.
Roberts WJ. A hypothesis on the physiological basis for causalgia and related pains. Pain 1986;24(3):297-311.
Ross JS, Robertson JT, Frederickson RC, Petrie JL, Obuchowski N, Modic MT, deTribolet N. Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. ADCON-L European Study Group. Neurosurgery 1996;38(4):855-861; discussion 861-853.
Shir Y, Seltzer Z. Effects of sympathectomy in a model of causalgiform pain produced by partial sciatic nerve injury in rats. Pain 1991;45(3):309-320.
Takebayashi T, Cavanaugh JM, Cuneyt Ozaktay A, Kallakuri S, Chen C. Effect of nucleus pulposus on the neural activity of dorsal root ganglion. Spine 2001;26(8):940-945.
Wall PD, Gutnick M. Ongoing activity in peripheral nerves: the physiology and pharmacology of impulses originating from a neuroma. Experimental neurology 1974;43(3):580-593.
Wei H, Jyvasjarvi E, Niissalo S, Hukkanen M, Waris E, Konttinen YT, Pertovaara A. The influence of chemical sympathectomy on pain responsivity and alpha 2-adrenergic antinociception in neuropathic animals. Neuroscience 2002;114(3):655-668.
Wheeler AH. Diagnosis and management of low back pain and sciatica. American family physician 1995;52(5):1333-1341, 1347-1338.
White DM, Basbaum AI, Goetzl EJ, Levine JD. The 15-lipoxygenase product, 8R,15S-diHETE, stereospecifically sensitizes C-fiber mechanoheat nociceptors in hairy skin of rat. Journal of neurophysiology 1990;63(5):966-970.
Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science (New York, NY 1989;246(4930):670-673.
Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L. Neutrophils: molecules, functions and pathophysiological aspects. Laboratory investigation; a journal of technical methods and pathology 2000;80(5):617-653.
Yabuki S, Kikuchi S, Olmarker K, Myers RR. Acute effects of nucleus pulposus on blood flow and endoneurial fluid pressure in rat dorsal root ganglia. Spine 1998;23(23):2517-2523.
Yildiz KH, Gezen F, Is M, Cukur S, Dosoglu M. Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model. Eur Spine J 2007.
Zuo Y, Perkins NM, Tracey DJ, Geczy CL. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 2003;105(3):467-479.
楊萬生 (指導老師:曾啟育, 簡基憲, 李世雄, 周一鳴). 椎板切除術後脊椎組織之病理形態學之研究. 碩士論文. 2006.