腰椎神經根病變表現型之機制

The Mechanisms Underlying Somatosensory Phenotypes of Lumbar radiculopathy

林建和(Jiann-Her Lin)

指導教授 ： 蔣永孝

共同指導教授 ： 陳志成 ； 王昀(Yun Wang)

臺北醫學大學/醫學科技學院/神經再生醫學博士學位學程/博士(2018年)

摘要

腰椎神經根病變 (Lumbar radiculopathy) 手術成功的關鍵在於了解不同解剖位置神經損傷會導致不同體感覺表徵。腰椎狹窄 (Lumbar stenosis) 所造成腰椎神經根病變的定義為背根、背根神經節 (dorsal root ganglion) 或脊神經的壓迫所導致的放射性下肢疼痛。腰椎狹窄根據解剖結構可分為中間型狹窄 (central stenosis) 或側邊狹窄 (lateral stenosis)，側邊狹窄包括背根神經節與其周圍神經組織的壓迫。此外，側邊狹窄又進一步分為側隱窩狹窄 (lateral recess stenosis) 或是椎間孔狹窄 (foraminal stenosis)，側隱窩狹窄是指背根神經節近端的神經組織被壓迫，椎間孔狹窄是指背根神經節遠端的神經組織被壓迫。某一解剖位置神經損傷所造成的體感覺表現，可能與另一解剖位置不同。本論文主要研究目的是探討腰椎神經根病變造成體感覺表徵的機制。藉由標準化定性感覺測試 (Standardized qualitative sensory test) 檢測六十位僅腰椎第五節脊神經有腰椎狹窄的患者，其中側邊狹窄患者的各項檢測顯示滿意的結果 (靈敏度= 0.455-0.727，特異性= 0.868-1.0)，證明側邊狹窄患者的感覺缺陷發生機率高於無側邊狹窄者 (45-73% 與 3-16%，p<0.0001)。在動物模型中，於背根神經節進行遠端神經結紮的疼痛持續時間比近端神經結紮長 (12週與4週的雙腳平衡測痛試驗，12週與7週為 50％ von-Frey 試驗，11週與4週的丙酮測試)。在免疫染色研究顯示，伴隨疼痛時間較長的背根神經節神經元，有更嚴重的缺氧與更多的神經元損傷，特別是 IB4+ 神經元。本論文結論為，背根神經節和其周圍神經組織的損傷與感覺缺陷相關，而背根神經節神經元缺氧與 IB4+ 神經元損傷的程度則與疼痛持續時間與強度相關。

關鍵字

腰椎神經根病變 ； 背根神經節 ； 慢性疼痛 ； 疼痛 ； 腰椎管狹窄

並列摘要

The knowledge of different somatosensory phenotypes in different anatomical locations of nerve injury is the key to a successful lumbar operation for lumbar radiculopathy (LR). LR associated with lumbar stenosis is defined as radiating leg pain related to the compression of dorsal root, or dorsal root ganglion (DRG), or spinal nerve. Lumbar stenosis is classified as central stenosis (CS) or lateral stenosis (LS) based on the anatomical structure and LS involved the compression of DRG and its surrounding nerve tissue. Moreover, LS is further divided into lateral recess stenosis (LRS) or foraminal stenosis (FS). The nerve tissues proximal or distal to DRG are compressed in LRS or FS, respectively. The somatosensory phenotype in one anatomical location of nerve injury may differ from that in another anatomical location. The aim of this thesis is to investigate the different somatophenotypes between different anatomical locations of nerve injury and, then, to probe the mechanisms underlying the somatosensory phenotypes in LR. Comparing LS with CS, patients with LS presented a higher incidence of sensory deficit than did those without LS (45-73% vs. 3-16%, p<0.0001). By using standardized qualitative sensory test (SQST) in the detection of symptomatic LS in 60 patients with lumbar stenosis involving only L5 spinal nerve, each item of the SQST showed a satisfactory performance in the detection of LS (sensitivity=0.455-0.727, specificity=0.868-1.0). The mechanism underlying the different somatophenotypes between LS-related LR and CS-related LR may be the presence of DRG injury in LS. Furthermore, comparing the somatophenotypes of LRS and FS, animals with nerve ligation distal to DRG showed longer pain duration than did those with nerve ligation proximal to DRG (12 vs. 4 weeks by incapacitence test, 12 vs. 7 weeks by 50% von-Frey test, 11 vs. 4 weeks by acetone test). The immunostaining study showed that more severe hypoxia and more neuron injury, specifically IB4 positive neurons, in DRG are associated with longer pain duration. In conclusion, the presence of DRG and its surrounding nerve tissue injury is associated with the presence of sensory deficit, and the level of and hypoxia and IB4+ DRG injury is associated with the duration and intensity of pain.

並列關鍵字

lumbar radiculopathy (LR) ； dorsal root ganglia (DRG) ； chronic pain ； pain ； lumbar stenosis

參考文獻

[1] A.W. Tarulli, E.M. Raynor, Lumbosacral radiculopathy, Neurologic clinics, 25 (2007) 387-405.

[2] K. Konstantinou, K.M. Dunn, Sciatica: review of epidemiological studies and prevalence estimates, Spine, 33 (2008) 2464-2472.

[5] M. Younes, I. Bejia, Z. Aguir, M. Letaief, S. Hassen-Zrour, M. Touzi, N. Bergaoui, Prevalence and risk factors of disk-related sciatica in an urban population in Tunisia, Joint, bone, spine : revue du rhumatisme, 73 (2006) 538-542.

[6] D.R. Murphy, E.L. Hurwitz, J.K. Gerrard, R. Clary, Pain patterns and descriptions in patients with radicular pain: does the pain necessarily follow a specific dermatome?, Chiropractic & osteopathy, 17 (2009) 9.

[7] J.S. Lipetz, Pathophysiology of inflammatory, degenerative, and compressive radiculopathies, Physical medicine and rehabilitation clinics of North America, 13 (2002) 439-449.