07-신재혁(우편교정)

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1 대한척추외과학회지제 13 권제 4 호 Journal of Korean Spine Surg. Vol. 13, No. 4, pp 275~283, 2006 추간판내장증에서추간판내로의신경침습 신재혁 서준영 하기용 가톨릭대학교의과대학강남성모병원정형외과 Nerve Ingrowth into Intervertebral Disc in Internal Disc Disruption Jae-Hyuk Shin, M.D., Joon-Yeong Seo, M.D., Kee-Yong Ha, M.D. Abstract Department of Orthopedic Surgery, Kang-Nam St. Mary s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Study Design: The ingrowth of the nociceptive nerve ending into intervertebral disc was examined using immunohistochemistry and quantified using western blotting. Objectives: To determine if the nociceptive nerve innervates into the intervertebral discs of internal disc disruption (IDD). Summary and Literature Review: Nociceptive nerve ending and vessel ingrowth into intervertebral disc is associated with IDD and HNP. Substance P is a neurotransmitter that is found in the nociceptive nerve endings. Immunohistochemistry has confirmed the presence, and western blot has isolated the target. The localization of novel nociceptive innervation, and a quantitative comparison was made according to the original pathology is of interest. Materials and Methods: 10 specimens of intervertebral disc were collected from IDD during total disc replacement surgery, and another 10 specimens of intervertebral disc from HNP were collected during discectomy. The control samples of intervertebral disc were obtained from 3 adolescent patients with idiopathic scoliosis, and 2 patients with a lumbar bursting fracture. Standard immunohistochemical techniques were used to test for the nociceptive neurotransmitter (substance P), which is a protein expressed during axonogenesis (growth-associated protein 43, GAP43), and a general nerve marker (protein gene produce 9.5, PGP9.5). The expression of substance P protein was quantified using western blot for its polyclonal antibody. Results: In IDD (n=10), substance P was expressed in 6 cases of outer annulus fibrosus (AF), 5 cases of inner AF, and 3 cases of nucleus pulposus (NP). In HNP (n=10), substance P was expressed in 4 cases of outer AF, 3 cases of inner AF, and 2 cases of NP. In the control group, only 2 cases expressed substance P in outer AF. GAP43 was only positive in outer AF as follows: IDD 3 cases, HNP 1 case, and control 1 case. None of the specimens showed localized PGP 9.5. Substance P was localized significantly in larger quantities in IDD than in the control group (p=0.002). In HNP, the expression level was larger than the control and lower than the IDD group but this was not statistically significant (p=0.158, p=0.108). Conclusions: Innervation of nociceptive nerve endings was identified at the degenerative intervertebral disc of IDD, which may contribute to back pain. Key Words: Intervertebral disc, Internal disc disruption, Herniated nucleus pulposus, Nociceptive nerve, Substance P Address reprint requests to Kee-Yong Ha, M.D. Department of Orthopaedic Surgery, Kang-Nam St. Mary s Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul, , Korea. Tel: , Fax: , kyh@catholic.ac.kr

2 대한척추외과학회지 Vol. 13, No. 4, 2006 서 론 요통의기전은신경근의압박에의하여발생될수있으나모든요통을이신경근압박으로만설명할수는없다. 자기공명영상에서신경근의압박소견이없어도요통을호소하는환자가있는데그원인으로추간판성요통의개념이보고되고있다 1,2,3). 이것은추간판의손상으로통각신경종말 (sensory nociceptive terminal) 의물리적자극이나퇴행성추간판에서분비되는화학적물질에의한자극에의해통증이유발된다는개념으로그정확한기전을밝히기위해많은연구가시행되고있다 1,2,3,4,5). 추간판성통증을이해하기위한추간판의신경분포에대한연구에서 Weinstein 등 3,4) 은추간공에위치한후근신경절이각운동분절의통증을조정하는기능을가진다고하였다. 즉섬유륜외측으로얽히게짜여진연속적 인신경섬유의망상조직이있는데이는앞쪽으로전방종인대의신경총에의해, 뒤쪽으로는후방종인대의신경총을통해나가서추간공에서서로연결되어교통지 (rami comunicantes) 를이룬다 6,7). Groen 등 7) 은이러한교통지가동척추신경과함께교감신경과밀접하게연관된다고하였고, Morinaga 등 8) 은이러한신경구조가교감신경의작용뿐만아니라일부에서감각신경의기능을가지고있다고하였다. 또한 Ashton 등 9) 은교감신경계가 C- 감각섬유와상호작용하여통각수용체 (nociceptor) 를감작시키는역할을한다고하였다. 조직학적검사에서정상적으로는종인대와섬유륜의표면층에신경종말이존재하고 1,10,11,12) 섬유륜의외측 1/3 까지신경이분포함이밝혀졌다 13). 그러나요통이있는환자에서섬유륜의손상에의해추간판내로신생혈관이생성되고그주위로신경섬유의증식이같이이루어진다는연구를통해추간판의병인을밝히고자하는시 Table 1. Patient Information Pt No. Age Sex Level Diagnosis Interval from Sx. onset to surgery IDD group M L5-S1 IDD 36 m M L4-5 IDD 24 m F L4-5 IDD 12 m F L5-S1 IDD 48 m M L4-5 IDD 05 m M L5-S1 IDD 60 m M L4-5 IDD 06 m F L3-5 IDD 48 m F L4-5 IDD 30 m F L5-S1 IDD 07 m HNP group F L4-5 HNP 002 d F L4-5 HNP 210 d M L4-5 HNP 210 d M L4-5 HNP 042 d F L4-5 HNP 010 d M L4-5 HNP 002 d M L4-5 HNP 005 d M L4-5 HNP 018 d F L5-S1 HNP 090 d M L5-S1 HNP 024 d Control group M L3-4 AIS F L3-4 AIS M L4-5 AIS M L4-5 BF M L3-4 BF (IDD, internal disc disruption; HNP, herniated nucleus pulposus; AIS, adolescent idiopathic scoliosis; BF, bursting fracture; m, months; d, days; Sx., symptom)

3 추간판내장증에서추간판내로의신경침습 신재혁외 도가진행되고있다 14,15,16). 따라서본논문의목적은추간판내장증에서추간판내의신경섬유의분포를관찰함으로써요통의병리기전을밝히고자하는것이다. 연구대상및방법 1. 조직의채취 10 예의요추추간판내장증환자에서인공추간판치환술시행시채취한 10 예의추간판과 10 예의요추부추간판탈출증환자로부터탈출된추간판제거술시채취한 10 예의추간판을대상으로하였다. 특히인공추간판치환술후채취한추간판은추간판절제시에채취한조직과가능한동일한조건을만들고자후방부위만을이용하였다. 추간판내장증환자의평균연령은 40.8 세 (24~51), 남성 5 예, 그리고여성 5 예였다. 분절부위는제 4-5 요추추간판이 5 예로가장많았고, 제 5 요추 - 제 1 천추추간판이 4 예, 그리고제 3-4 요추추간판이 1 예였다 (Table 1). 전예에서요통을호소하였다. 자기공명영상상변성된추간판의추간판조영술에서조영제주입시평소와 일치된통증 (concordant pain) 이재연되는경우추간판절제술을시행하였다. 증상발현후수술까지걸린기간은평균 27.6 개월로 5 개월로부터 60 개월까지다양하였다. 추간판내장증환자에서추간판조영술시평소와일치 된통증을호소한환자의 MRI 상 90% 에서중등도내지고도의추간판의퇴행성변화가있었고 10% 에서경도의퇴행성변화가있었다. 60% 에서 high intensity zone 양성이었으며 80% 에서추간판의높이감소와종판 (end plate) 의이상이있었고, 50% 에서중등도혹은고도의후관절낭골관절염소견이있었다. 또한모든환자에서추간판의파열이존재하였고조영제의추간판외로의누출소견을관찰할수있었다 (Fig. 1, Table 2). 추간판탈출증환자의평균연령은 29.9(19~40) 세였으며이중남성 6 예, 여성 4 예였다. 분절부위는제 4-5 요추추간판이 8 예, 그리고제 5 요추 - 제 1 천추추간판이 2 예였다. 모든예에서심한하지방사통을호소하였으며증상발현부터수술까지기간은평균 61 일로써 2 일에서 210 일까지였다. 대조군은 3 예의청소년기특발성측만증과 2 예의방출성골절에서전방고정술및기기고정술시채취한추간판을대상으로하였다. 평균연령은 25.6(10~45) 세였고남성 4 예, 여성 1 예였으며분절부위는제 3-4 요추추간판 3 예, 그리고제 4-5 요추추간판 2 예였다 (Table 1). 모든조직은채취즉시액화질소에보관후, 실험시까지 -70 에서보관하였다. 2. 조직학적관찰및 Western blot 1) 면역조직화학적관찰수술시채취한추간판을대상으로 10% neutral Fig. 1. CT discography shows leakages of dye. Intervertebral disc specimens is obtained from the indicated area by rectangle (A). MRI of the same patient shows the degeneration of intervertebral disc of L4-5, L5-S1 and the hight intensity zone (B)

4 대한척추외과학회지 Vol. 13, No. 4, 2006 Table 2. MR and CT Discographic Findings of IDD (HIZ, High Intensity Zone) No.* Concordant pain MRI grade HIZ Decreased End plate abnormality Facet osteoarthritis + Discography ++ disc height (Modic type**) (grade) I 2 V V V I 2 V I 2 V III 3 V III 1 V I 1 V III 1 V II 1 V * : the same numbering as Table 1. : grade 3. mild degeneration, blurred differentiation of the nucleus pulposus from the annulus, slightly decreased signal of the nucleus pulposus with minor irregularities; grade 4, moderate disc degeneration, blurred differentiation of the nucleus pulposus from the annulus, moderately decreased signal of the nucleus pulposus, with hypointense zones; grade 5, severe degeneration, a loss of differentiation of the nucleus pulposus from the annulus, hypointense signal of the nucleus pulposus with or without a horizontal hyperintense band. : focal zone of high signal intensity within the posterior aspect of the annulus fibrosus, without focal protrusion or extrusion of the disc. ** : type I, low signal intensity of T1-weighted images and high signal intensity on T2-weighted images; type II, high signal intensity on both images; type III, low signal intensity on both images. + : grade 1, mild degenerative disease(indicated by narrowing of the facet joint space, small osteophytes, and/or mild hypertrophy of the articular process); grade 2, moderate degenerative disease(indicated by narrowing of the facet joint space, moderate osteophytes, moderate hypertrophy of the articular process, and/or mild subarticular erosions); grade 3, severe degenerative disease(indicated by narrowing of the facet joint space, severe osteophytes, severe hypertrophy oh the articular process, severe subarticular erosions, and/or subchondral cysts). ++ : type I, cottonball; type II, lobular; type III, irregular; type IV, fissured; type V, ruptured. buffered formalin 에고정하고파라핀포매조직을 3 μm 로잘라슬라이드에부착시킨후 60 C 신전기에서 1 시간조직이떨어지지않도록부착시켰다. 조직이부착된슬라이드를 xylene 3 단계로탈파라핀화하였고다시함수과정을거친후트리스완충액 (tris-buffer) 으로처리후내인성 peroxidase 의활성을억제시키기위하여 3% H 2 O 2 - methanol 용액에 10 분간반응시켰다. 비특이적인항원 - 항체결합을방지하기위해 normal horse serum 에 15 분간반응시킨뒤 1:1000 으로희석된일차항체 polycolonal Substance P antibody(santa Cruz Biotechnology, Santa Cruz, CA), mouse anti-gap43(mouse anti-growth associated protein 43, Zymed, South San Francisco, CA), mouse-antihuman PGP9.5(mouse-antihuman protein gene product 9.5, Serotec, Oxford, UK) 로 4 C 에서 16 시간동안반응시켰다. 뒤에 biotin 이부착된이차항체 (R.T.U vectastain Kit: Vector, Burlingame, CA) 로실온에서 20 분간반응시킨후발색제 DAB(diamino-benzidine) 5~10 분간반응시키고 hematoxylin 으로대조염색하여검체조직에서발현되는특정단백질의존재여부와그위치를관찰하였다. 2) Western blot 12.5% 의 SDS-PAGE(sodium dodecyl sulfate polyacrylamide gel electrophoresis) 에전기영동하여단백질을크기별로분리한후 PVDF(polyvinylidene fluoride) membrane 에 100 V 에서 1 시간동안전환하였다. PVDF(polyvinylidene fluoride) membrane 을 Ponceau S(Ponceau S 2g, trichloroacetic acid 30g, sulfosalicylic acid 30g) 용액에 5 분정도반응시킨후증류수로씻어내어전환된단백질을확인하였다. 단백질이확인된 PVDF(polyvinylidene fluoride) membrane 을 5% skimmilk 이용하여 2 시간동안여백에비특이적항체의결합을방지한후 3% skimmilk 용액에 polycolonal Substance P antibody(santa Cruz technology) 를 1: 100 으로첨가하여 4 C 에서 16 시간동안반응시킨후 peroxidase labeled anti-goat? antibody(santa Cruz technology) 를이차항체로이용하여반응시켰다. ECL(enhanced chemiluminescence) Kit(RPN 2108, Amersham Pharmacia Biotech, Buckinghamshire, UK) 을이용하여감광하여결과를확인하고감광의정도를 Image Analyzer LAS-3000 의 Multi Gauge software 를이용하여흡광도를측정하였다

추간판내장증에서추간판내로의신경침습 신재혁외 3. 통계적분석 western blotting 에서발현된 substance P 의상대적양을 optical density 로측정하여추간판내장증및추간판탈출증에서의통계학적유의를위하여일원배치분산분석 (one-way ANOVA; SPSS 11.

5 추간판내장증에서추간판내로의신경침습 신재혁외 3. 통계적분석 western blotting 에서발현된 substance P 의상대적양을 optical density 로측정하여추간판내장증및추간판탈출증에서의통계학적유의를위하여일원배치분산분석 (one-way ANOVA; SPSS 11.0 for windows) 및다중비교 (multiple comparison; SPSS 11.0 for windows) 를이용하여검증하였다. 측에서 6 예, 내측에서 5 예, 그리고 3 예가수핵내에서발현되었다. 10 예의추간판탈출증환자에서는섬유륜외측에서 4 예, 내측에서 3 예그리고수핵 2 예에서발현되었으며 (Fig. 2), 대조군에서는섬유륜외측에서 2 예관찰되었다. 그러나 GAP43 은추간판내장증과추간판탈출증환자의섬유륜외측에서만각각 3 예와 1 예씩관찰할수있었고 (Fig. 3), 대조군에서도섬유륜외측에서만 1 예에서관찰되었다. PGP9.5 는섬유륜과수핵에서모두발현되지않았다 (Table 3). 결 과 2. Western blot 을이용한 substance P 의정량분석결과 1. Substance P, GAP43 및 PGP9.5 에대한면역조직화학염색 substance P 는 10 예의추간판내장증환자의섬유륜외 동일한정량에서의 substance P 의발현을 western blotting 을이용하여얻은 band 를 optical density(od) 를측정하여분석한결과대조군에서의평균 OD 는 5,843.42± 2, 이었으며, 추간판탈출증에서의평균 OD 는 Fig. 2. Photomicrographs showing evidence of innervation in internal disc disruption. SP-immunoreactive nerve fiber is present in outer one third of the annulus fibrosus (arrows in A and B), and in the nucleus pulposus, with longitudinal (open arrows in C and D) and cross (arrows in E and F) section. (SP: substance P)

대한척추외과학회지 Vol. 13, No. 4, 2006 Fig. 3. (A, B) GAP43-immunoreactive nerve fiber (arrow) is present in the annulus fibrosus of IDD (A) and of HNP (B). Table 3. Substance P-, GAP43- and PGP9.

6 대한척추외과학회지 Vol. 13, No. 4, 2006 Fig. 3. (A, B) GAP43-immunoreactive nerve fiber (arrow) is present in the annulus fibrosus of IDD (A) and of HNP (B). Table 3. Substance P-, GAP43- and PGP9.5-immunoreactive fibers in the groups of discs. IDD, n=10; HNP, n=10, Control, n=5. Substance P GAP43 PGP9.5 Control IDD HNP Control IDD HNP Control IDD HNP Outer 1/3 of AF Inner 2/3 of AF NP (AF, annulus fibrosus; NP, nucleus pulposus; IDD, internal disc disruption; HNP, herniated nucleus pulposus.) 10,408.83±5, 이었으며, 추간판내장증에서의평균 OD 는 15,483.67±3, 이었다. 일원배치분산분석 (one-way ANOVA) 및 Scheffe 의다중비교결과추간판내장증과대조군과는유의한차이가있었으나 (p IDDcontrol=0.002) 추간판탈출증은대조군및추간판내장증과유의한차이가없었다 (p HNP-control =0.158, P IDD-HNP =0.108) (Fig. 4). 고 찰 Fig. 4. Westen blots and statistical analysis. Statistically significantly more expression of substance P in IDD than control group (p IDD-control=0.002) (one-way ANOVA; SPSS 11.0 for windows). 추간판의신경분포에대해다양한소재가연구되고있는데그대상이동물대인간, 그리고태아에서성인까지광범위하여일반적인결론유추가난해하였다. 그러나이들연구의공통점은요추간판의신경분포는섬유륜의외측에국한된다는것이다. 구조상으로섬유륜후부가손상에취약한부분으로평가되는데추간판조영술을시행한후에전산화단층촬영을시행한연구에서조영제가수핵으로부터섬유륜후부의파열된틈을통해새어나오는것을관찰하였다 16). 이러한섬유륜의손상을복구하려는생리적반응으로혈관생성을동반한육아조직의증식이나타나게된다. 정상적으로는성인의추간판에는혈관이없으나실험적연구에서육아조직형성에의해치유된섬유륜조직에서혈관이관찰되었다 15). 또손상된돼지추간판의연구에서수술후 2 주에서 2 개월간섬유륜의치유된부위에서모세혈관의조밀한망상조직을관찰할수있

7 추간판내장증에서추간판내로의신경침습 신재혁외 었고 14), 사람의퇴행성추간판내부로의신생혈관생성도보고되었다 17). 이러한섬유륜의손상을복구하는과정으로생성된염증성육아조직은 IL-6, IL-8, PGE2같은 inflammatory cytokines를분비하고이것이추간판내에서통각수용체를감작시키는중재물질의역할을하는것으로알려져있다 18). substance P는 nociceptive pain mediator로서 19) 실제로 Gile과 Harvey 20), Ashton 등 9) 은사람의후관절낭에서 substance P를포함한신경을발견하였고, Korkala 등 21) 은후종인대에서도 substance P의면역반응성을관찰하였고, 쥐의추간판연구에서섬유륜의외측과극간인대에서 substance P, calcitonin gene related peptide(cgrp), vasoactive intestinal peptide(vip) 를발현하는신경섬유가있음을확인하였다 3,4,22). Ashton 등 23) 은요통이없는사람의추간판외측 3 mm내에서 substance P, CGRP, VIP 를확인하였으나 Coppes 등 24) 은퇴행성추간판에서는내측에서도 substance P를발현하는신경섬유를관찰하였다. 또한 Freemont 등 25) 도이환된추간판의내측에서 substance P를발현하는신경섬유를관찰하였으며최근에 Peng 등 26) 은통증을호소하는추간판의파열된틈을따라형성된육아조직부위를따라섬유륜의내부와수핵까지 substance P, neurofilament, VIP를발현하는신경섬유가자라들어오는것을관찰하였다. Freemont 등 25) 은만성요통이있는환자에서요추추간판의전방부위에서조직을채취하였으며섬유륜의바깥 1/3에서 60% 에서신경섬유를발견하였고섬유륜의내부 1/3 및수핵내로각각46% 와 22% 에서신경섬유가자라들어가는것을관찰하였다. 그러나일반적으로추간판조영술시행시전방부위의균열의발생은드물다. 따라서이들의실험은요통의원인으로설명하기는부족하다. 따라서 Peng 등 26) 은후방부위에서조직을채취한후 substance P, NF, VIP - immunoreactive nerve fiber가대조군보다증가하였다고하였다. 이는추간판성요통및추간판조영술의원인으로추간판후방조직에신경지배가중요한역할을한다고하였다. 저자들은추간판내장증과수핵탈출증의추간판을채취시동일한조건을얻고자후방부위만선택하여실험을시행하였다. 또한본연구에서는추간판내장증환자와추간판탈출증환자의추간판에서면역염색화학법을이용하여섬유륜의내부와수핵에서의 substance P에반응하는신경섬유를관찰하였다. substance P와같이사용한 PGP9.5는일반적인신경표지자이고 GAP43은축삭형성 (axonogenesis) 시발현하는단백질이다. Freemont 등 25) 은실험에서추간판내부에는두가지형태의신경섬유가있는데하나는혈관과같이주행하는신경섬유이고다른하나는단독으로주행하는신경섬유가있는데단독으로 주행하는신경섬유가통각신경종말의형태를가진것이라하였다. 또한이들은 PGP9.5 와 substance P 가혈관과같이주행하는신경섬유에서발현하는것을관찰하였고 GAP43 은이러한신경섬유에서는발현하지않았으며단독주행하는신경섬유에서만발현하는것을관찰하였다. 또한 substance P 가단독으로주행하는신경섬유에서도발현하는것으로관찰되었다. 본연구에서는단독으로주행하는신경섬유만이 substance P 와 GAP43 을이용한면역화학염색에서발현되는것을관찰할수있었다. 채취한추간판을실험에사용하기위해일부분만절제하는과정에서비교적손상되지않은부분을선택하였기때문에혈관생성을동반한육아조직이발견되지않았고이러한이유로신생혈관주위에서발견될수있는 PGP9.5 를발현하는신경섬유는관찰할수없었던것으로생각된다. 면역화학염색법에서 substance P 와 GAP43 을발현하는신경섬유는추간판내장증환자에서더많이발현되었으며 western blots 을시행하여추간판내장증환자에서 substance P 에반응한단백의양이대조군에비해많음 (p IDD-control =0.002) 을밝혀냄으로서요통성추간판에통각신경섬유가많이분포하는이유를입증하였다. 추간판내장증과추간판탈출증, 그리고추간판탈출증과대조군은각각차이는있었으나통계적으로유의하지는않았다 (pidd-hnp=0.108, phnp-control=0.158). 또한추간판의퇴행성변화에의한신생혈관이자라들어감과함께신경섬유가침입하여요통의병인과추간판내로의신경침습이상호연관되어있음을알게되었다. 면역조직화학염색법을이용한신경섬유의관찰에대한연구는많았으나 western blots 을시행하여정량적분석을시도한연구를시행하였다는점에본논문의의의가있다. 그러나본연구에서대조군으로방출성골절과특발성측만증에서의추간판을사용하였는데, 방출성골절의경우골절이연골종판까지연장되어파괴되었다면추간판에큰영향을미칠것으로생각되며, 또한정상추간판으로간주하기어렵다는제한이있었다. 또한특발성측만증의경우에서도정상추간판과비교하여기질의조성및구조차이와연골종판석회화에따른투과성감소등이있어이환기간과환자의연령에따라추간판의변성이이미있을수있다는점도고려해야할것이다. 참고문헌 01) Hirsch C, Ingelmark BE, Miller M: The anatomical basis for low back pain. Studies on the presence of sensory nerve endings in ligamentous, capsular and intervertebral

8 대한척추외과학회지 Vol. 13, No. 4, 2006 disc structures in the human lumbar spine. Acta Orthop Scand 1963; 33: ) Bogduk N, Windsor M, Inglis A: The innervation of the cervical intervertebral discs. Spine 1988;13: ) Weinstein J, Claverie W, Gibson S: The pain of discography. Spine 1988;13: ) Weinstein J, Pope M, Schmidt R, Seroussi R: Neuropharmacologic effects of vibration on the dorsal root ganglion. An animal model. Spine 1988;13: ) Stolker RJ, Vervest AC, Groen GJ: The management of chronic spinal pain by blockades: a review. Pain 1994;58: ) Bleys RL, Groen GJ, Matthijssen MA: A method for identifying peripheral connections of perivascular nerves based on sensitive acetylcholinesterase staining via perfusion. J Histochem Cytochem 1994;42: ) Groen GJ, Baljet B, Drukker J: Nerves and nerve plexuses of the human vertebral column. J Anat 1990; 188: ) Morinaga T, Takahashi K, Yamagata M, et al: Sensory innervation to the anterior portion of lumbar intervertebral disc. Spine 1996 Aug 15; 21: ) Ashton IK, Ashton BA, Gibson SJ, Polak JM, Jaffray DC, Eisenstein SM: Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. J Orthop Res 1992; 10: ) Pedersen HE, Blunck CF, Gardner E: The anatomy of lumbosacral posterior rami and meningeal branches of spinal nerve (sinu-vertebral nerves); with an experimental study of their functions. J Bone Joint Surg 1956; 38-A: ) Malinsky J: The ontogenetic development of nerve terminations in the intervertebral discs of man. (Histology of intervertebral discs, 11th communication). Acta Anat (Basel) 1959; 38: ) Jackson HC, Winkelmann RK, Bickel WH: Nerve endings in the human lumbar spinal column and related structures. J Bone Joint Surg 1966; 48-A: ) Yoshizawa H, O'Brien JP, Smith WT, Trumper M: The neuropathology of intervertebral discs removed for lowback pain. J Pathol 1980; 132: ) Kaapa E, Gronblad M, Holm S, Liesi P, Murtomaki S, Vanharanta H: Neural elements in the normal and experimentally injured porcine intervertebral disk. Eur Spine J 1994; 3: ) Osti OL, Vernon-Roberts B, Fraser RD: 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 1990; 15: ) Saifuddin A, Braithwaite I, White J, Taylor BA, Renton P: The value of lumbar spine magnetic resonance imaging in the demonstration of anular tears. Spine 1998; 23: ) Vernon-Roberts B, Fazzalari NL, Manthey BA: Pathogenesis of tears of the anulus investigated by multiplelevel transaxial analysis of the T12-L1 disc. Spine 1997; 22: ) Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM: Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br. 2002; 84: ) Henry JL: Relation of substance P to pain transmission: neurophysiological evidence. Ciba Found Symp. 1982; (91): ) Giles LG, Harvey AR: Immunohistochemical demonstration of nociceptors in the capsule and synovial folds of human zygapophyseal joints. Br J Rheumatol 1987; 26: ) Korkala O, Gronblad M, Liesi P, Karaharju E: Immunohistochemical demonstration of nociceptors in the ligamentous structures of the lumbar spine. Spine 1985; 10: ) McCarthy PW, Petts P, Hamilton A: RT97- and calcitonin gene-related peptide-like immunoreactivity in lumbar intervertebral discs and adjacent tissue from the rat. J Anat 1992; 180 : ) Ashton IK, Roberts S, Jaffray DC, Polak JM, Eisenstein SM: Neuropeptides in the human intervertebral disc. J Orthop Res 1994; 12: ) Coppes MH, Marani E, Thomeer RT, Groen GJ: Innervation of "painful" lumbar discs. Spine 1997; 22: ) 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: ) Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y: The pathogenesis of discogenic low back pain. J Bone Joint Surg Br Jan; 87:

9 추간판내장증에서추간판내로의신경침습 신재혁외 국문초록 연구계획 : 통각신경섬유 (nociceptive nerve fiber) 의추간판내로의신생분지를면역조직화학법을이용하여확인하고, western blot을이용하여정량비교분석하였다. 연구목적 : 추간판내장증에서추간판내의통각신경섬유 (nociceptive nerve fiber) 의분포를관찰함으로써요통의병리기전을밝히고자하였다. 대상및방법 : 요추추간판내장증환자의추간판절제술에서 10예의추간판과요추추간판탈출증의수핵제거술에서 10예의추간판을채취하였다. 대조군으로 3예의청소년기특발성측만증과 2예의방출성골절에서채취된추간판을이용하였다. 면역조직화학염색법으로통각신경전달물질인 substance P, 축삭형성시발현되는단백질인 growthassociated protein 43(GAP43), 일반신경표지자인 protein gene product 9.5 (PGP9.5) 를확인하였다. 그리고 western blots 을이용하여 substance P의발현을정량분석비교하였다. 결과 : substance P 는추간판내장증 (10예) 의섬유륜외측에서 6예, 내측에서 5예, 수핵에서 3예발현되었고, 추간판탈출증 (10예) 에서는섬유륜외측에서 4예, 내측에서 3예, 수핵에서 2예발현되었다. 대조군 (5예) 에서는섬유륜외측에서만 2예에서발견되었다. GAP43은섬유륜외측에서만추간판내장증, 추간판탈출증, 그리고대조군에서각각 3예, 1예, 그리고 1예관찰되었다. PGP9.5는모든예에서발현되지않았다. western blots에서추간판내장증과대조군과는 substance P의발현에유의한차이가있었으나 (P=0.002) 추간판탈출증은대조군보다는높게, 추간판내장증군보다는낮게나타났으나통계적유의지않았다 (p=0.158, p=0.108). 결론 : 추간판내장증에서요통의기전으로퇴행성변화에의한추간판의손상으로추간판내부로통각신경종말 (nociceptive nerve endings) 의침습을확인할수있었다. 색인단어 : 추간판, 추간판내장증, 추간판탈출증, 통각신경, Substance P 통신저자 : 하기용서울특별시서초구반포동 505번지가톨릭대학교의과대학, 강남성모병원정형외과 Tel: Fax: kyh@catholic.ac.kr

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical