过度运动对肱二头肌长头肌腱组织形态学和生物力学及其周围组织神经分布影响的实验研究
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摘要
目的：研究肩关节过度运动对肱二头肌长头肌腱组织形态学和生物力学及
其周围组织神经分布的影响，探讨肩关节疾病的发病机理，为预防、诊断和
治疗肩关节疾病提供理论依据。
方法：建立SD大鼠双侧肩关节过度运动模型，分别于过度运动后4周、8
周后处死动物，取材。以HE和Alcian blue染色，观测肱二头肌长头肌腱组
织形态学及细胞外基质的变化；通过改良银染法和免疫组织化学的方法，研
究肱二头肌长头肌腱周围组织神经末梢分布情况以及P物质免疫阳性神经纤
维的变化；将完整肱二头肌长头肌腱连肩肿骨取下，在室温下以4mm/min的
速度，在拉伸仪上做轴向拉伸实验，在4次加载-卸载预调后，拉伸肌腱至断
裂，记录肌腱所能承受的最大载荷，计算肌腱所能耐受的最大应力，比较对
照组和实验各组肌腱所能耐受的最大载荷和最大应力。对以上结果进行统计
学分析。
结果：正常和异常肱二头肌长头肌腱在肉眼观察下未见有明显差异，肌
腱色泽均匀，呈亮白色，和周围组织无粘连。正常肱二头肌长头肌腱纵切面
可见规则平行排列的胶原纤维和呈梭形的健细胞。过度运动后在肱二头肌长
头肌腱对应小结节的部位胶原纤维丧失了正常的排列结构，腱细胞的形态呈
软骨样改变，形成纤维软骨样结构。肌腱的横截面积在过度运动8周后明显
变小；过度运动后肌腱所能耐受的最大载荷和最大应力均有显著的减低。通
过改良银染以及免疫组织化学方法的检测，结果发现肱二头肌长头肌腱本身
并没有神经分布，但在其周围组织上则有部分神经末梢的分布。在过度运动
前后腱鞘上神经末梢数量无明显改变，但P物质免疫反应阳性神经末梢数量
第四军医大学硕士学鳅文
一
明显增加。
结论：由于结节间沟的特殊形态结构，在肩关节过度运动时会对肪二头
肌长头肌腥组织学及生物力学特性产生影响。在肌健和肪骨接触最多的部位
产生纤维软骨样结构，同时该部位细胞外基质也发生改变，氨基己糖多糖含
量明显增加，同时肌健对抗张应力的能力下降，使肌健更容易受损伤。大鼠
肽二头肌长头肌健本身并无神经的分布，但其健鞘却有神经末梢分布，并有
少数神经纤维存在。健鞘在过度运动后在组织形态学上无明显的改变，无炎
症细胞出现，神经末梢的数量也无明显改变，但P物质兔疫反应阳性神经末
梢数量明显增加，而P物质正是传导和调控疼痛并介导局部炎症的神经肽。
以上这些研究说明过度运动增高了脑二头肌长头肌攘及其周围组织发生撕裂
和炎症的风险性，会导致肩关节疼痛，是肩关节疾病的重要诱发因素。
Objective: To study the influence of overuse activity on the shoulder joint
disease by morphology, biomechanics and nerve distribution of the long head of
biceps tendon and paratendon tissue in rat models, so as to to investigate the
etiology of the shoulder disease and provide a theory basis for prevention, diagnosis
and therapy for the shoulder disease. Methods:Overuse animal model was
established in Sprague-Dawley rats. 24 Sprague-Dawley rats was randomly divided
into two groups ,and experienced 4 weeks and 8 weeks overuse respectively with
bilateral shoulder joints, and then killed them to achieve the long head of biceps
tendons and paratendon tissues.The tendon samples were studied by HE and Alcian
blue stain to investigate the changes of the histology and the extracellular matrix.
The nerve distribution of tendons and paratendon tissues were investigated by
modified silver and immunohistochemistiy stain and the sbustance P-
immunoreactive nerve endings were detected. The long head of biceps tendons
were got with the scapulae integratedly and then were clamped to the tensile divice
at room temperature with the constant tensile rate of 4mm/mm. After 4 load-
download tests, the tendons were loaded until ruptured. The maxium loads were
recorded, and the maximun stresses were calculated, and the maximun loads and the
maximun stresses were compared between the experiment groups and the controls.
Result:There bad no obviously difference between the normal and the overused
tendons to the naked eye. They appeared glistening white and had no adhesion with
the surrounding tissues. Under microscopy, regular parallel bundles of coll \v..拻-.\..>扸??N<.. <.2
-3-
fibres and spindle shaped tendon cells were found in the longitudinal section of
the normal tendons. After overuse activity, the tendon lost their normal structure at
the site where the tendon faced the lesser tubercle and showed some structural
features of fibrous cartilage. The ovoid chondrocyte-like cells in the tendon were
also found, and in this area glycosaminoglycans were increased obviously. After 8
weeks of overuse, the area of the tendons?cross section apparently declined (p and the maximun load and the maximun stress decreased significently (p compared with the normals. Through modified silver and immunohistochemistry
stain, we found no nerve distribution in the tendon themselves, but found that there
had some nerve endings in the paratendon tissues. There had no obviously
difference on the mounts of the nerve endings between the normal and the overused
tendons,but the mounts of the substance P-imniunoreactive nerve endings increased
signifieently. Conclusion:Because of the special structure of the intertubercular
sulcus, there will have some effect on the histology and the biomechanics of the
long head of biceps tendons when shoulder joints have overuse activities. In order
to adapt to the pressure and shearing force, The parts facing the humerus show
some changes of flbrocartilage with the increase of glycosaminoglycans. This
changes decline the capability of against tensile force of the tendons, so the tendons
became easier to be damaged. The mounts of the substance P-immunoreactive
nerve endings increase significently after overuse activity and that substance P is a
neuropeptide which can not only transmit and control pain, but also mediate local
inflammation. These researches show that overuse activity can increase the risk of
trauma and inflammation of the long
其周围组织神经分布的影响，探讨肩关节疾病的发病机理，为预防、诊断和
治疗肩关节疾病提供理论依据。
方法：建立SD大鼠双侧肩关节过度运动模型，分别于过度运动后4周、8
周后处死动物，取材。以HE和Alcian blue染色，观测肱二头肌长头肌腱组
织形态学及细胞外基质的变化；通过改良银染法和免疫组织化学的方法，研
究肱二头肌长头肌腱周围组织神经末梢分布情况以及P物质免疫阳性神经纤
维的变化；将完整肱二头肌长头肌腱连肩肿骨取下，在室温下以4mm/min的
速度，在拉伸仪上做轴向拉伸实验，在4次加载-卸载预调后，拉伸肌腱至断
裂，记录肌腱所能承受的最大载荷，计算肌腱所能耐受的最大应力，比较对
照组和实验各组肌腱所能耐受的最大载荷和最大应力。对以上结果进行统计
学分析。
结果：正常和异常肱二头肌长头肌腱在肉眼观察下未见有明显差异，肌
腱色泽均匀，呈亮白色，和周围组织无粘连。正常肱二头肌长头肌腱纵切面
可见规则平行排列的胶原纤维和呈梭形的健细胞。过度运动后在肱二头肌长
头肌腱对应小结节的部位胶原纤维丧失了正常的排列结构，腱细胞的形态呈
软骨样改变，形成纤维软骨样结构。肌腱的横截面积在过度运动8周后明显
变小；过度运动后肌腱所能耐受的最大载荷和最大应力均有显著的减低。通
过改良银染以及免疫组织化学方法的检测，结果发现肱二头肌长头肌腱本身
并没有神经分布，但在其周围组织上则有部分神经末梢的分布。在过度运动
前后腱鞘上神经末梢数量无明显改变，但P物质免疫反应阳性神经末梢数量
第四军医大学硕士学鳅文
一
明显增加。
结论：由于结节间沟的特殊形态结构，在肩关节过度运动时会对肪二头
肌长头肌腥组织学及生物力学特性产生影响。在肌健和肪骨接触最多的部位
产生纤维软骨样结构，同时该部位细胞外基质也发生改变，氨基己糖多糖含
量明显增加，同时肌健对抗张应力的能力下降，使肌健更容易受损伤。大鼠
肽二头肌长头肌健本身并无神经的分布，但其健鞘却有神经末梢分布，并有
少数神经纤维存在。健鞘在过度运动后在组织形态学上无明显的改变，无炎
症细胞出现，神经末梢的数量也无明显改变，但P物质兔疫反应阳性神经末
梢数量明显增加，而P物质正是传导和调控疼痛并介导局部炎症的神经肽。
以上这些研究说明过度运动增高了脑二头肌长头肌攘及其周围组织发生撕裂
和炎症的风险性，会导致肩关节疼痛，是肩关节疾病的重要诱发因素。
Objective: To study the influence of overuse activity on the shoulder joint
disease by morphology, biomechanics and nerve distribution of the long head of
biceps tendon and paratendon tissue in rat models, so as to to investigate the
etiology of the shoulder disease and provide a theory basis for prevention, diagnosis
and therapy for the shoulder disease. Methods:Overuse animal model was
established in Sprague-Dawley rats. 24 Sprague-Dawley rats was randomly divided
into two groups ,and experienced 4 weeks and 8 weeks overuse respectively with
bilateral shoulder joints, and then killed them to achieve the long head of biceps
tendons and paratendon tissues.The tendon samples were studied by HE and Alcian
blue stain to investigate the changes of the histology and the extracellular matrix.
The nerve distribution of tendons and paratendon tissues were investigated by
modified silver and immunohistochemistiy stain and the sbustance P-
immunoreactive nerve endings were detected. The long head of biceps tendons
were got with the scapulae integratedly and then were clamped to the tensile divice
at room temperature with the constant tensile rate of 4mm/mm. After 4 load-
download tests, the tendons were loaded until ruptured. The maxium loads were
recorded, and the maximun stresses were calculated, and the maximun loads and the
maximun stresses were compared between the experiment groups and the controls.
Result:There bad no obviously difference between the normal and the overused
tendons to the naked eye. They appeared glistening white and had no adhesion with
the surrounding tissues. Under microscopy, regular parallel bundles of coll \v..拻-.\..>扸??N<.. <.2
-3-
fibres and spindle shaped tendon cells were found in the longitudinal section of
the normal tendons. After overuse activity, the tendon lost their normal structure at
the site where the tendon faced the lesser tubercle and showed some structural
features of fibrous cartilage. The ovoid chondrocyte-like cells in the tendon were
also found, and in this area glycosaminoglycans were increased obviously. After 8
weeks of overuse, the area of the tendons?cross section apparently declined (p
stain, we found no nerve distribution in the tendon themselves, but found that there
had some nerve endings in the paratendon tissues. There had no obviously
difference on the mounts of the nerve endings between the normal and the overused
tendons,but the mounts of the substance P-imniunoreactive nerve endings increased
signifieently. Conclusion:Because of the special structure of the intertubercular
sulcus, there will have some effect on the histology and the biomechanics of the
long head of biceps tendons when shoulder joints have overuse activities. In order
to adapt to the pressure and shearing force, The parts facing the humerus show
some changes of flbrocartilage with the increase of glycosaminoglycans. This
changes decline the capability of against tensile force of the tendons, so the tendons
became easier to be damaged. The mounts of the substance P-immunoreactive
nerve endings increase significently after overuse activity and that substance P is a
neuropeptide which can not only transmit and control pain, but also mediate local
inflammation. These researches show that overuse activity can increase the risk of
trauma and inflammation of the long
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72． Duplla H,Chassaing G,Lavielle S, et al.Influence of the replacement of amino acid by its D-enantioner in the sequence of substance P.1． Binding and pharmacological data. Neuropeptides. 1992,19:251-75
73． Igwe OJ,Kim DC,Seybold,VS,et al.Specific bonding of substance P aminoterminal heptapeptide[SP(l-7) ] to mouse brain and spinal cord membranes.J Neurosci. 1990,10:3653-63
74． Dugga A,Hendry IA,Green JL,et al.The preparation and use of antibody microprobes.J Neurosci Meth.l990,23:241-243
75． Zhao ZQ,Yang HQ,Zhang KM,et al.Release and depletion of substance P by capsaicin in substantia gelatinosa studied with the antidody microprobe technique and immunohistochemistry. Neuropeptides. 1992,23:161-167
76． Chen JJ, Barber LA, Dymshitz J. Peptidase inhibitors improve recovery of substance P and calcitonin gene-related peptide release from rat spinal cord slices. Peptides. 1996,17(l):31-7
77． Kream RM, Kato T, Shimonaka H, Marchand JE, Wurm WH. Substance P markedly potentiates the antinociceptive effects of morphine sulfate administered at the spinal level. Proc Natl Acad Sci USA. 1993 Apr 15;90(8) :3564-8
78． 浦波,胡侦明.腰背疼痛与神经肽P物质.中国脊柱脊髓杂志 .2000,10( 4) :245-6
79． De Koninck Y, Ribeiro-da-Silva A, Henry JL, Cuello AC. Spinal neurons exhibiting a specific nociceptive response receive abundant substance P-containing synaptic contacts. Proc Natl Acad Sci USA. 1992 Jun l;89(11) :5073-7
80． 朱丽霞,黎春元,吉长福。P物质在脊髓水平痛觉传递与痛觉调制中的双重作用。中国科学(B辑), 1986, 12: 1285-1294
81． Gallai V, Sarchielli P, Trequattrini A, Paciaroni M. Monocyte chemotactic and phagocytic responses in migraine and tension-type headache patients. Ital J Neurol Sci. 1993 Mar,14(2) : 153-64
82． Blum AM, Elliott DE, Metwali A, Li J.Substance P regulates somatostatin expression in inflammation. J Immunol. 1998 Dec 1,161(11) :6316-22
83． Schaffer M, Beiter T, Becker HD, Hunt TK. Neuropeptides: mediators of inflammation and tissue repair? Arch Surg. 1998 Oct, 133(10) :1107-16
84． Stanisz AM, Befus D, Bienenstock J. Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J Immunol. 1986 Jan;136(l): 152-6
85． Kahler CM, Pischel A, Kaufmann G, Wiedermann CJ. Influence of neuropeptides on neutrophil adhesion and transmigration through a lung fibroblast barrier in vitro. Exp Lung Res. 2001 Jan-Feb,27(1) :25-46
86． Lau AH, Chow SS, Ng YS. Immunologically induced histamine release from rat peritoneal mast cells is enhanced by low levels of substance P. Eur J Pharmacol. 2001 Mar 2,414(2-3) :295-303
87． Matsuda H, Kawakita K, Kiso Y. Substance P induces granulocyte infiltration through degranulation of mast cells. J Immunol. 1989 Feb 1;142(3) :927-31
88． Levite M. Nerve-driven immunity. The direct effects of neurotransmitters on T-cell function. Ann N Y Acad Sci. 2000, 917:307-21
89． Shadiack AM, Carlson CD, Ding M. Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic interleukin-1 production. J Neuroimmunol. 1994 Jan; 49(1-2) : 51-8
90． Limmroth V, Cutrer FM, Moskowitz MA. Neurotransmitters and neuropeptides
in headache.Curr pin Neurol. 1996 Jun, 9(3) : 206-10
91． Marukawa H, Shimomura T, Takahashi K. Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in migraine and tension-type headache. Headache. 1996 Feb, 36(2) : 100-04
92． DiSabato F, Giacovazzo M, Cristalli G, et al. Effect of hyper-baric oxygen on the immunoreactivity to substance P in the nasal mucosa of cluster headache patients.Headache. 1996 Apr; 36 (4) :221-3
93． Fusco BM, Fiore G, Gallo F, et al. "Capsaicin-sensitive" sensory neurons in cluster headache: pathophysiological aspects and therapeutic indication. Headache. 1994 Mar,34(3) : 132-7
94． Ahmed M, Bjurholm A, Schultzberg M, et al. Increased levels of substance P and calcitonin gene-related peptide in rat adjuvant arthritis. Arthritis Rheum. 1995,38:699-709
95． Fortier LA, Nixon AJ: Distributional changes in substance P nociceptive fiber patterns in naturally osteoarthritic articulations. J Rheumatol. 1997,24:524-530
96． Heppelmann B, Pawlak M: Sensitisation of articular afferents in normal and inflamed knee joints by substance P in the rat. Neurosci Lett. 1997,223:97-100
97． Ide K, Shirai Y, Ito H, Ito H. Sensory nerve supply in the human subacromial bursa. J Shoulder Elbow Surg. 1996,5:371-382
98． McDougall JJ, Bray RC, Sharkey KA: Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat Rec. 1997,248:29-39
99． Santavirta S, Konttinen YT, Antti-Poika I, et al. Inflammation of the subacromial bursa in chronic shoulder pain. Arch Orthop Trauma Surg. 1992,111:336-340
100． Tomita Y, Ozaki J, Sakurai G,et al. Neurohistory of the subacromial bursa in rotator cuff tear. J Orthop Sci. 1997,2:295-300
101． Kaneko H, Mitsuma T, Uchida K,et al. Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease.Am J Gastroenterol .1993 Jun, 88(6) :898-904
102． Pfahler M, Branner S, Refior HJ. The role of the bicipital groove in tendopathy of the long bicepss tendon. J Shoulder Elbow Surg. 1999 Sep-Oct, 8(5) : 419-24
103． Refior HJ, Sowa D. Long tendon of the bicepss brachii: sites of predilection for degenerative lesions. J Shoulder Elbow Surg. 1995 Nov-Dec,4(6) :436-40
104． Riley GP, Harrall RL, Constant CR. Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis. 1994 Jun, 53(6) : 367-76
105． Li BY. The effect of glycosaminoglycans in the pulmonary interstitial fibrosis development. Chung Hua Chieh Ho Ho Hu His Tsa Chih. 1992 Aug, 15(4) : 204-6, 253-4
106． Szende B, Lapis K, Kovalszky I. Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in the CC14-induced fibrosis of the rat liver. In-Vivo. 1992 Jul-Aug, 6(4) : 355-61
107． Freemont AJ, Peacock TE, Goupille P. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997 Jul 19,350 (9072) : 178-81
108． Beaman DN,Graziano GP,Glover RA,et al.Substance P innervation of lumbar spine facet joints. Spine.l993,18(8) :1044-1049．
109． Bohy A,Cavanaugh JM,Getchell ML,et al.Localization of substance P and neurofilament immunoreactive fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. Brain Res.l988,20,460(2) :379-382．
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71． Tregear GW, Niall HD, Potts JT Jr. Synthesis of substance P. Nat New Biol. 1971 Jul 21;232(29) :87-9
72． Duplla H,Chassaing G,Lavielle S, et al.Influence of the replacement of amino acid by its D-enantioner in the sequence of substance P.1． Binding and pharmacological data. Neuropeptides. 1992,19:251-75
73． Igwe OJ,Kim DC,Seybold,VS,et al.Specific bonding of substance P aminoterminal heptapeptide[SP(l-7) ] to mouse brain and spinal cord membranes.J Neurosci. 1990,10:3653-63
74． Dugga A,Hendry IA,Green JL,et al.The preparation and use of antibody microprobes.J Neurosci Meth.l990,23:241-243
75． Zhao ZQ,Yang HQ,Zhang KM,et al.Release and depletion of substance P by capsaicin in substantia gelatinosa studied with the antidody microprobe technique and immunohistochemistry. Neuropeptides. 1992,23:161-167
76． Chen JJ, Barber LA, Dymshitz J. Peptidase inhibitors improve recovery of substance P and calcitonin gene-related peptide release from rat spinal cord slices. Peptides. 1996,17(l):31-7
77． Kream RM, Kato T, Shimonaka H, Marchand JE, Wurm WH. Substance P markedly potentiates the antinociceptive effects of morphine sulfate administered at the spinal level. Proc Natl Acad Sci USA. 1993 Apr 15;90(8) :3564-8
78． 浦波,胡侦明.腰背疼痛与神经肽P物质.中国脊柱脊髓杂志 .2000,10( 4) :245-6
79． De Koninck Y, Ribeiro-da-Silva A, Henry JL, Cuello AC. Spinal neurons exhibiting a specific nociceptive response receive abundant substance P-containing synaptic contacts. Proc Natl Acad Sci USA. 1992 Jun l;89(11) :5073-7
80． 朱丽霞,黎春元,吉长福。P物质在脊髓水平痛觉传递与痛觉调制中的双重作用。中国科学(B辑), 1986, 12: 1285-1294
81． Gallai V, Sarchielli P, Trequattrini A, Paciaroni M. Monocyte chemotactic and phagocytic responses in migraine and tension-type headache patients. Ital J Neurol Sci. 1993 Mar,14(2) : 153-64
82． Blum AM, Elliott DE, Metwali A, Li J.Substance P regulates somatostatin expression in inflammation. J Immunol. 1998 Dec 1,161(11) :6316-22
83． Schaffer M, Beiter T, Becker HD, Hunt TK. Neuropeptides: mediators of inflammation and tissue repair? Arch Surg. 1998 Oct, 133(10) :1107-16
84． Stanisz AM, Befus D, Bienenstock J. Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. J Immunol. 1986 Jan;136(l): 152-6
85． Kahler CM, Pischel A, Kaufmann G, Wiedermann CJ. Influence of neuropeptides on neutrophil adhesion and transmigration through a lung fibroblast barrier in vitro. Exp Lung Res. 2001 Jan-Feb,27(1) :25-46
86． Lau AH, Chow SS, Ng YS. Immunologically induced histamine release from rat peritoneal mast cells is enhanced by low levels of substance P. Eur J Pharmacol. 2001 Mar 2,414(2-3) :295-303
87． Matsuda H, Kawakita K, Kiso Y. Substance P induces granulocyte infiltration through degranulation of mast cells. J Immunol. 1989 Feb 1;142(3) :927-31
88． Levite M. Nerve-driven immunity. The direct effects of neurotransmitters on T-cell function. Ann N Y Acad Sci. 2000, 917:307-21
89． Shadiack AM, Carlson CD, Ding M. Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic interleukin-1 production. J Neuroimmunol. 1994 Jan; 49(1-2) : 51-8
90． Limmroth V, Cutrer FM, Moskowitz MA. Neurotransmitters and neuropeptides
in headache.Curr pin Neurol. 1996 Jun, 9(3) : 206-10
91． Marukawa H, Shimomura T, Takahashi K. Salivary substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in migraine and tension-type headache. Headache. 1996 Feb, 36(2) : 100-04
92． DiSabato F, Giacovazzo M, Cristalli G, et al. Effect of hyper-baric oxygen on the immunoreactivity to substance P in the nasal mucosa of cluster headache patients.Headache. 1996 Apr; 36 (4) :221-3
93． Fusco BM, Fiore G, Gallo F, et al. "Capsaicin-sensitive" sensory neurons in cluster headache: pathophysiological aspects and therapeutic indication. Headache. 1994 Mar,34(3) : 132-7
94． Ahmed M, Bjurholm A, Schultzberg M, et al. Increased levels of substance P and calcitonin gene-related peptide in rat adjuvant arthritis. Arthritis Rheum. 1995,38:699-709
95． Fortier LA, Nixon AJ: Distributional changes in substance P nociceptive fiber patterns in naturally osteoarthritic articulations. J Rheumatol. 1997,24:524-530
96． Heppelmann B, Pawlak M: Sensitisation of articular afferents in normal and inflamed knee joints by substance P in the rat. Neurosci Lett. 1997,223:97-100
97． Ide K, Shirai Y, Ito H, Ito H. Sensory nerve supply in the human subacromial bursa. J Shoulder Elbow Surg. 1996,5:371-382
98． McDougall JJ, Bray RC, Sharkey KA: Morphological and immunohistochemical examination of nerves in normal and injured collateral ligaments of rat, rabbit, and human knee joints. Anat Rec. 1997,248:29-39
99． Santavirta S, Konttinen YT, Antti-Poika I, et al. Inflammation of the subacromial bursa in chronic shoulder pain. Arch Orthop Trauma Surg. 1992,111:336-340
100． Tomita Y, Ozaki J, Sakurai G,et al. Neurohistory of the subacromial bursa in rotator cuff tear. J Orthop Sci. 1997,2:295-300
101． Kaneko H, Mitsuma T, Uchida K,et al. Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease.Am J Gastroenterol .1993 Jun, 88(6) :898-904
102． Pfahler M, Branner S, Refior HJ. The role of the bicipital groove in tendopathy of the long bicepss tendon. J Shoulder Elbow Surg. 1999 Sep-Oct, 8(5) : 419-24
103． Refior HJ, Sowa D. Long tendon of the bicepss brachii: sites of predilection for degenerative lesions. J Shoulder Elbow Surg. 1995 Nov-Dec,4(6) :436-40
104． Riley GP, Harrall RL, Constant CR. Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis. 1994 Jun, 53(6) : 367-76
105． Li BY. The effect of glycosaminoglycans in the pulmonary interstitial fibrosis development. Chung Hua Chieh Ho Ho Hu His Tsa Chih. 1992 Aug, 15(4) : 204-6, 253-4
106． Szende B, Lapis K, Kovalszky I. Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in the CC14-induced fibrosis of the rat liver. In-Vivo. 1992 Jul-Aug, 6(4) : 355-61
107． Freemont AJ, Peacock TE, Goupille P. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997 Jul 19,350 (9072) : 178-81
108． Beaman DN,Graziano GP,Glover RA,et al.Substance P innervation of lumbar spine facet joints. Spine.l993,18(8) :1044-1049．
109． Bohy A,Cavanaugh JM,Getchell ML,et al.Localization of substance P and neurofilament immunoreactive fibers in the lumbar facet joint capsule and supraspinous ligament of the rabbit. Brain Res.l988,20,460(2) :379-382．
110． Brown MF,Hukkanen MV,McCarthy ID,et al.Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease.J Bone Joint Surg Br.l997,79(l): 147-153．