1.Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury.
Daisuke NOJIMA ; Kazuhide INAGE ; Yoshihiro SAKUMA ; Jun SATO ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Nobuyasu OCHIAI ; Kazuki KUNIYOSHI ; Yasuchika AOKI ; Junichi NAKAMURA ; Masayuki MIYAGI ; Miyako SUZUKI ; Gou KUBOTA ; Takeshi SAINOH ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Gen INOUE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Yonsei Medical Journal 2016;57(3):748-753
PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.
Animals
;
Antibodies
;
Calcitonin Gene-Related Peptide/metabolism
;
Disease Models, Animal
;
Ganglia, Spinal/*metabolism
;
Intervertebral Disc/*drug effects/*injuries
;
Intervertebral Disc Degeneration/metabolism
;
Low Back Pain/*physiopathology
;
Lumbar Vertebrae/injuries
;
Male
;
NAV1.7 Voltage-Gated Sodium Channel/*metabolism
;
Neurons/*metabolism
;
Pain/metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Stilbamidines
2.Relationship between lumbosacral multifidus muscle and lumbar disc herniation.
Wei-ye CHEN ; Kuan WANG ; Wei-an YUAN ; Hong-sheng ZHAN
China Journal of Orthopaedics and Traumatology 2016;29(6):581-584
As a common disease in clinical, the treatment of lumbar disc herniation (LDH) focused on local intervertebral disc, such as surgery and other interventional therapy treatment, but postoperative complications and recurrence rate has been a difficult problem in the field of profession. With the development of spine biomechanics and anatomy, researches on lumbar herniation also increased. Researchers discovered that the incidence and prognosis of LDH were inseparable with local muscle and soft tissue. As the deep paraspinal muscles, multifidus muscle plays an important role to make lumbar stability. Its abnormal function could reduce the stable of lumbar spine, and the chronic lumbar disease could also lead to multifidus muscle atrophy.
Animals
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Humans
;
Intervertebral Disc Displacement
;
physiopathology
;
surgery
;
Lumbosacral Region
;
physiopathology
;
surgery
;
Paraspinal Muscles
;
physiopathology
3.Case-control study on three spinal rotation manipulations for the treatment of lumbar disc herniation.
Hong-gen DU ; Hui WEI ; Zhong JIANG ; Huan-ming WANG ; Shu-liang YE ; Hong-quan SONG ; Xi-tao NING
China Journal of Orthopaedics and Traumatology 2016;29(5):444-448
OBJECTIVETo evaluate the efficacy and safety of three different spinal rotation manipulations for the treatment of lumbar disc herniation.
METHODSFrom September 2011 to April 2013,180 patients diagnosed as lumbar disc herniation were randomly divided into seat fixed rotation group (A), lateral position rotation group (B) and supine position rotation group (C) by using a digital table. Finally 10 patients were excluded and dropped, 170 patients were included in the study. There were 57 patients in group A, 57 patients in group B and 56 patients in group C. Baseline demographic characteristics of patients, clinical findings and indexes of health status had no statistically differences among three groups (P > 0.05). The manipulation was performed every other day, and the treatment duration for all patients was 3 weeks. Body pain (BP), Physical function (PF) in SF-36, Oswestry Disability Index (ODI) and adverse reactions were observed statistically 6 weeks, 3 months, 6 months, one year and two years after finishing treatment.
RESULTSBP, PF scores in 3 groups were significantly improved and ODI scores were significantly lower than those before treatment and the differences were statistically significant (P < 0.05); However, there was no significant difference among three groups in the BP, PF and ODI scores (P > 0.05). There were no obvious and serious adverse reactions among these groups.
CONCLUSIONBased on the theory of dislocation of bone joints in TCM, three kinds of spinal rotation manipulations can be used safely for the treatment of lumbar disc herniation, and the efficacy was similar.
Adolescent ; Adult ; Case-Control Studies ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; therapy ; Male ; Manipulation, Spinal ; methods ; Middle Aged ; Rotation ; Treatment Outcome ; Young Adult
4.Biomechanical analysis on the correlation between iliac rotation displacement and L(4,5) disc degeneration.
Ning-ning SHI ; Guo-quan SHEN ; Shui-yong HE ; Ru-bao GUO
China Journal of Orthopaedics and Traumatology 2016;29(5):439-443
OBJECTIVETo study the biomechanical relationship between iliac rotation displacement and L(4,5) disc degeneration, and to provide clinical evidences for the prevention and treatment of L(4,5) disc degeneration and herniation.
METHODSFrom March 2012 to February 2014,68 patients with lumbar disc herniation combined with sacroiliac joint disorders were selected. Among them, 42 patients with L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78 +/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc herniation combined with sacroiliac joint disorders included 11 males and 15 females, ranging in age from18 to 65 years old with an average of (45.53 +/- 27.23) years old, and the duration of the disease ranged from 0.5 to 103 months with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken. The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc thickness were studied by using linear and regression methods. The hiomechanical analysis was performed.
RESULTSThere was a positive correlation between pelvic tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49, P=0.00). There was a causal relationship and good linear proportional relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative correlation between lumbar scoliosis and intervertebral space in male patients with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship and good linear proportional relationship in the two variables (Y=13.09-0.27X, P=0.02). But there was a positive correlation between lumbar scoliosis and intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04).
CONCLUSIONIliac rotational displacement are closely related with L(4,5) disc degeneration and herniation in biomechanics. A new concepts and therapeutic approach is provided for clinical treatment of chronic and refractory herniation of L(4,5) disc in patients
Adult ; Biomechanical Phenomena ; Female ; Humans ; Intervertebral Disc Degeneration ; physiopathology ; Intervertebral Disc Displacement ; physiopathology ; Lumbar Vertebrae ; physiopathology ; Male ; Rotation ; Sacroiliac Joint ; chemistry ; physiopathology ; Young Adult
5.Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in Ex vivo Organ Culture.
Li-Guo ZHU ; Min-Shan FENG ; Jia-Wen ZHAN ; Ping ZHANG ; Jie YU
Chinese Medical Journal 2016;129(19):2338-2346
BACKGROUNDThe development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ.
METHODSIVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues.
RESULTSThe results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content.
CONCLUSIONSA loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we were able to study the effects of mechanical stimulation on the biology of IVDs, as well as the pathomechanics of IVD degeneration.
Animals ; Gene Expression Regulation ; Immunohistochemistry ; Intervertebral Disc ; metabolism ; physiology ; Intervertebral Disc Degeneration ; metabolism ; physiopathology ; Male ; Nucleus Pulposus ; metabolism ; physiology ; Organ Culture Techniques ; methods ; Rabbits ; Stress, Mechanical
6.Cervical Interlaminar Epidural Steroid Injection for Unilateral Cervical Radiculopathy: Comparison of Midline and Paramedian Approaches for Efficacy.
Ji Young YOON ; Jong Won KWON ; Young Cheol YOON ; Jongseok LEE
Korean Journal of Radiology 2015;16(3):604-612
OBJECTIVE: The objective of this study was to compare the clinical outcomes of the cervical interlaminar epidural steroid injection (CIESI) for unilateral radiculopathy by the midline or paramedian approaches and to determine the prognostic factors of CIESI. MATERIALS AND METHODS: We retrospectively analyzed 182 patients who underwent CIESI from January 2009 to December 2012. Inclusion criteria were no previous spinal steroid injection, presence of a cross-sectional image, and presence of follow-up records. Exclusion criteria were patients with bilateral cervical radiculopathy and/or dominant cervical axial pain, combined peripheral neuropathy, and previous cervical spine surgery. Short-term clinical outcomes were evaluated at the first follow-up after CIESI. We compared the clinical outcomes between the midline and paramedian approaches. Possible prognostic factors for the outcome, such as age, gender, duration of radiculopathy, and cause of radiculopathy were also analyzed. RESULTS: Cervical interlaminar epidural steroid injections were effective in 124 of 182 patients (68.1%) at the first follow-up. There was no significant difference in the clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%) approaches (p = 0.723). Cause of radiculopathy was the only significant factor affecting the efficacy of CIESI. Patients with disc herniation had significantly better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p < 0.001). CONCLUSION: There is no significant difference in treatment efficacy between the midline and paramedian approaches in CIESI, for unilateral radiculopathy. The cause of the radiculopathy is significantly associated with the treatment efficacy; patients with disc herniation experience better pain relief than those with neural foraminal stenosis.
Adrenal Cortex Hormones/*therapeutic use
;
Adult
;
Aged
;
Cervical Cord/physiopathology
;
Cross-Sectional Studies
;
Female
;
Humans
;
Injections, Epidural
;
Intervertebral Disc Displacement/*drug therapy/radiography
;
Male
;
Middle Aged
;
Radiculopathy/*drug therapy/radiography
;
Retrospective Studies
;
Treatment Outcome
7.Treatment of low lumbar degenerative disease with unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation.
Rong-Xue SHAO ; Peng LUO ; Yan LIN ; Hua-Zi XU ; Yong-Long CHI
China Journal of Orthopaedics and Traumatology 2015;28(4):318-322
OBJECTIVETo explore the operative skills and effect of unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation in treating degenerative low lumbar disease.
METHODSFrom January 2009 to December 2011,22 patients with degenerative low lumbar disease were treated with transforaminal lumbar interbody fusion, during the operations, unilateral pedicle screw and contralateral percutaneous transfacet screw fixation were performed. There were 16 males and 6 females, aged from 32 to 71 years old with an average of (51.1 ± 10.6) years, including single segment in 20 cases and two segments in 2 cases. Clinical effects were evaluated according to visual analogue score (VAS) and Oswestry Disability Index (ODI).
RESULTSAll patients were followed up from 1 to 2.5 years with an average of 18 months. One case complicated with leakage of cerebrospinal fluid after operation and 1 case with lower limb pain of decompression-side on the 3rd day after operation. Twenty-two patients got bony fusion. There were no instability and evidence of instrument failure during follow-up. The VAS and ODI score decreased from preoperative 8.24 ± 0.72, 36.72 ± 6.84 respectively to 3.18 ± 0.66, 4.36 ± 1.12 at the final follow-up (P < 0.05).
CONCLUSIONUnilateral pedicle screw combined with contralateral percutaneous transfacet screw fixation is safe and feasible surgical technique in treating low lumbar degenerative disease. It has advantages of little trauma, rigid fixation, high fusion rate, and less complication. etc.
Adult ; Aged ; Biomechanical Phenomena ; Female ; Humans ; Intervertebral Disc Degeneration ; physiopathology ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Spinal Fusion ; methods
8.Mid-term effect of unilateral pedicle screw fixation and transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases.
Liang-Le LIU ; Ming-Hai DAI ; Xiao-Jun TANG ; Gang-Yi JIANG ; Cheng-Xuan TANG ; Li-Cheng ZHANG
China Journal of Orthopaedics and Traumatology 2015;28(4):313-317
OBJECTIVETo investigate the feasibility and the mid-term effects of unilateral pedicle screw fixation and transforaminal lumbar interbody fusion in treating lumbar degenerative diseases.
METHODSFrom August 2005 to May 2010, 56 patients with lumbar degenerative diseases underwent lumbar posterolateral fusion,their clinical data were retrospective analyzed. The patients were divided into two groups (unilateral group and bilateral group) according to fixation methods,27 patients in unilateral group who were underwent unilateral pedicle screw fixation, including 18 males and 9 females with a mean age of (57.5 ± 7.1) years old (ranged from 41 to 66 years); and 29 patients in bilateral group who were treated with bilateral pedicle screw fixation (on the basis of the above, with contralateral vertebral pedicle screw fixation), including 19 males and 10 females with a mean age of (54.6 ± 5.1) years old (ranged from 43 to 68 years). The clinical data such as operation time, blood loss volume, hospitalization time and cost were compared between two groups. JOA score system was used to evaluate the neurological function. And fusion status and cage-related complication were also analyzed.
RESULTSAll patients were followed up from 36 to 60 months with an average of 45.8 months. No iatrogenic nerve, blood vessels or organs injury were found during operation. Operation time, blood loss volume, hospitalization time and cost in unilateral group were better than that of bilateral group (P < 0.05). There was no significant difference in JOA score between two groups (P > 0.05). Two patients in unilateral group developed with cage related complications, 1 case was cage displacement and 1 case was cage subsidence, while 2 patients in bilateral group developed with complications of no-fusion, and there was no significant differences between two groups (P = 0.58).
CONCLUSIONUnilateral pedicle screw fixation is a satisfactory method and can obtain good effects in treating lumbar degenerative diseases in mid-term, however, the indications should be well considered.
Adult ; Aged ; Biomechanical Phenomena ; Female ; Humans ; Intervertebral Disc Degeneration ; physiopathology ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Spinal Fusion ; methods
9.Research advance on intervertebral disc degeneration and cell death.
Tao-tao XU ; Fei LIAO ; Hong-ting JIN ; Pei-jian TONG ; Lu-wei XIAO ; Cheng-liang WU
China Journal of Orthopaedics and Traumatology 2015;28(7):673-678
Intervertebral disc degeneration is considered as a primary cause of clinical low back pain, however the molecular mechanism is not clear yet. Recently, researches on the molecular basis of intervertebral disc degeneration have become a hotspot. The special structure and biomechanics properties of the disc contribute to its propensity toward degeneration. Intervertebral disc degeneration is associated with the changes of the cytological behavior,including the increase in cell death and the degradation of extracellular matrix. However, the mechanism of cell death including cell apoptosis and autophagy in intervertebral disc degeneration remains unclear. Further study on the molecular mechanism of intervertebral disc degeneration is the foundation of improving and treating the intervertebral disc degeneration in the future. Although some progresses are made in the aspect of biological study, the biological environment of intervertebral disc itself is still a challenge for the development of biological treatment. This article is to review the latest advance on the biological characteristics of normal intervertebral disc and the cell death in the process of the intervertebral disc degeneration.
Animals
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Apoptosis
;
Cell Death
;
Extracellular Matrix
;
metabolism
;
Humans
;
Intervertebral Disc
;
cytology
;
metabolism
;
Intervertebral Disc Degeneration
;
metabolism
;
physiopathology
10.Effect of spinal manipulation on brain functional activity in patients with lumbar disc herniation.
Wei-an YUAN ; Zhi-bi SHEN ; Li XUE ; Wen-li TAN ; Ying-wu CHENG ; Song-hua ZHAN ; Hong-sheng ZHAN ;
Journal of Zhejiang University. Medical sciences 2015;44(2):124-137
OBJECTIVETo investigate the effects of spinal manipulation (SM) on brain functional activity in patients with lumbar disc herniation (LDH).
METHODSEleven patients with LDH were recruited in the study. All patients received 6 times of lumbar SM treatment and then clinical efficacy was evaluated. All patients received brain functional magnetic resonance imaging (fMRI) scans before and after SM treatment.
RESULTSThree subjects dropped out and 8 subjects completed the study, among whom 4 cases were effective and 4 ineffective after SM treatment. The required pressure value producing the same level (VAS 50) pain was (7.43 ± 1.47) kg and (10.53 ± 0.55) kg before and after SM treatment in effective patients(P<0.05); however, there was no significant difference in ineffective patients (P>0.05). Compared to pre-treatment level, the brain functional activity in effective patients was mainly inhibited, the inhibited areas were located in the right side of prefrontal cortex and cerebellum; while the brain functional activity was generally enhanced in ineffective patients.
CONCLUSIONSM can affect the brain functional activity of patients with LDH, the inhibited areas is mainly located in prefrontal cortex and cerebellum when SM treatment is effective.
Brain ; physiopathology ; Humans ; Intervertebral Disc Displacement ; therapy ; Lumbar Vertebrae ; pathology ; Magnetic Resonance Imaging ; Manipulation, Spinal

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