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.Effects of Danshensu on bone formation in ovariectomized rats.
Tao QU ; Ping ZHENG ; Chengwei YANG ; Xu LAN ; Tao ZHANG ; Hua LIU ; Shiyong WANG
Journal of Zhejiang University. Medical sciences 2016;45(6):587-591
To investigate the effects of Danshensu on bone formation in ovariectomized rats.Thirty female SD rats were randomly divided into three groups with 10 rats in each:blank control group, model control group and Danshensu group. The osteoporosis model was induced by bilateral ovariectomy and rats in Danshensu group were fed with Danshensu 12.5 mg·kg·dby gavage after ostroporosis model induced. All animals were sacrificed after 90 days. The bone mineral density (BMD) of the whole body, femur and lumbar vertebra was measured by dual energy X-ray absorptiometry. The biomechanical properties of femur were measured by AG-IS mechanical universal testing machine. Serum osteocalcin and bone alkaline phosphates (BALP) levels were measured by ELISA. The number of osteoblasts of proximal femoral metaphysis was counted with light microscopy after HE staining.Compared with blank control group, BMD, biomechanical properties of femur, serum osteocalcin and BALP levels and the number of osteoblasts were decreased in model control group (<0.05 or<0.01). While compared with model control group, BMDs of the whole body, femur and lumbar vertebra, the elastic modulus, maximum load, yield strength, breaking point load of femur, the serum levels of osteocalcin and BALP, and the number of osteoblasts were significantly improved in Danshensu group (<0.05 or<0.01).Danshensu can improve bone quality by increasing bone density, improving biomechanical properties, promoting the expression of osteogenesis-related factors, and increasing the number of osteoblasts.
Alkaline Phosphatase
;
blood
;
drug effects
;
Animals
;
Biomechanical Phenomena
;
drug effects
;
Bone Density
;
drug effects
;
Cell Count
;
Female
;
Femur
;
anatomy & histology
;
cytology
;
drug effects
;
Lactates
;
pharmacology
;
Lumbar Vertebrae
;
anatomy & histology
;
drug effects
;
Osteoblasts
;
drug effects
;
Osteocalcin
;
blood
;
drug effects
;
Osteogenesis
;
drug effects
;
Osteoporosis
;
drug therapy
;
Ovariectomy
;
Rats
;
Rats, Sprague-Dawley
3.Effects of icariin total flavonoids capsule on bone mineral density and bone histomorphometry in growing rats.
Yuhai GAO ; Fangfang YANG ; Huirong XI ; Wenyuan LI ; Ping ZHEN ; Keming CHEN
Journal of Zhejiang University. Medical sciences 2016;45(6):581-586
To investigate the effect of icariin total flavonoids capsules (ITFC) on bone mineral density (BMD) and bone histomorphometry in growing rats and its anti-osteoporosis mechanism.Thirty female SD rats were randomly divided into 3 groups:normal control group, ITFC-1 group and ITFC-2 group. Rats in ITFC-1 group and ITFC-2 group were fed with 50 mg·kg·dor 100 mg·kg·dITFC, respectively, and those in normal control group were fed with equal volume of distilled water. The whole body BMD was measured after 4, 8 and 12 weeks, and BMDs of the right femur and lumbar vertebrae were measured after 12 weeks. The serum levels of tartaric acid phosphatase 5b (TRACP 5b) and bone alkaline phosphatase (BALP) were measured by ELISA. Bone morphometry was performed on the right tibia.There were no significant differences in the body weight increase between normal control group and two ITFC groups (all>0.05). There were also no significant differences in whole body BMDs after 4 and 8 weeks between normal control group and ITFC groups (all>0.05). After 12 weeks, the whole body BMD, BMD of bone, serum BALP level and trabecular area in ITFC-1 group and ITFC-2 group were significantly higher, trabecular separation was significantly lower than that in normal control group (all<0.05); and the trabecular width and the number in ITFC-2 group were also significantly higher, and serum TRACP 5b level was significantly lower than that in normal control group (all<0.05). The BMD of bone, serum BALP level, trabecular number and area in ITFC-2 group were significantly higher, and serum TRACP 5b level was significantly lower than that in ITFC-1 group (all<0.05).ITFC can prevent osteoporosis by increasing bone density and bone formation, decreasing bone resorption and improving microstructure of bone.
Alkaline Phosphatase
;
blood
;
drug effects
;
Animals
;
Bone Density
;
drug effects
;
Bone Resorption
;
drug therapy
;
Cancellous Bone
;
anatomy & histology
;
Dose-Response Relationship, Drug
;
Female
;
Femur
;
anatomy & histology
;
Flavonoids
;
pharmacology
;
Lumbar Vertebrae
;
anatomy & histology
;
Osteogenesis
;
drug effects
;
Osteoporosis
;
prevention & control
;
Rats
;
Rats, Sprague-Dawley
;
growth & development
;
Tartrate-Resistant Acid Phosphatase
;
blood
;
drug effects
;
Tibia
;
anatomy & histology
4.Paralytic Ileus and Prophylactic Gastrointestinal Motility Medication after Spinal Operation.
Chang Hyun OH ; Gyu Yeul JI ; Seung Hwan YOON ; Dongkeun HYUN ; Hyeong Chun PARK ; Yeo Ju KIM
Yonsei Medical Journal 2015;56(6):1627-1631
PURPOSE: To investigate the prevalence of paralytic ileus after spinal operation in the supine or prone operative position and to determine the efficacy of prophylactic gastrointestinal motility medications in preventing symptomatic paralytic ileus after a spinal operation. MATERIALS AND METHODS: All patients received spinal surgery in the supine or prone operative position. The study period was divided into two phases: first, to analyze the prevalence of radiographic and symptomatic paralytic ileus after a spinal operation, and second, to determine the therapeutic effects of prophylactic gastrointestinal motility medications (postoperative intravenous injection of scopolamine butylbromide and metoclopramide hydrochloride) on symptomatic paralytic ileus after a spinal operation. RESULTS: Basic demographic data were not different. In the first phase of this study, 27 patients (32.9%) with radiographic paralytic ileus and 11 patients (13.4%) with symptomatic paralytic ileus were observed. Radiographic paralytic ileus was more often noted in patients who underwent an operation in the prone position (p=0.044); whereas the occurrence of symptomatic paralytic ileus was not different between the supine and prone positioned patients (p=0.385). In the second phase, prophylactic medications were shown to be ineffective in preventing symptomatic paralytic ileus after spinal surgery [symptomatic paralytic ileus was observed in 11.1% (4/36) with prophylactic medication and 16.7% (5/30) with a placebo, p=0.513]. CONCLUSION: Spinal surgery in the prone position was shown to increase the likelihood of radiographic paralytic ileus occurrence, but not symptomatic paralytic ileus. Unfortunately, the prophylactic medications to prevent symptomatic paralytic ileus after spine surgery were shown to be ineffective.
Adjuvants, Anesthesia/*administration & dosage/pharmacology
;
Adult
;
Aged
;
Antiemetics/*administration & dosage/pharmacology
;
Female
;
Gastrointestinal Motility/*drug effects/physiology
;
Humans
;
Injections, Intravenous
;
Intestinal Pseudo-Obstruction/drug therapy/epidemiology/*prevention & control
;
Lumbar Vertebrae/radiography/*surgery
;
Male
;
Metoclopramide/*administration & dosage/pharmacology
;
Middle Aged
;
Postoperative Complications/epidemiology
;
Prevalence
;
Prone Position
;
Prospective Studies
;
Republic of Korea
;
Scopolamine Hydrobromide/*administration & dosage/*pharmacology
;
Spinal Fusion/*adverse effects
;
Supine Position
;
Treatment Outcome
5.Percutaneous Vertebroplasty of the Entire Thoracic and Lumbar Vertebrae for Vertebral Compression Fractures Related to Chronic Glucocorticosteriod Use: Case Report and Review of Literature.
Qing Hua TIAN ; Chun Gen WU ; Quan Ping XIAO ; Cheng Jian HE ; Yi Feng GU ; Tao WANG ; Ming Hua LI
Korean Journal of Radiology 2014;15(6):797-801
Glucocorticosteroid-induced osteoporosis is the most frequent of all secondary types of osteoporosis, and can increase the risk of vertebral compression fractures (VCFs). There are promising additions to current medical treatment for appropriately selected osteoporotic patients. Few studies have reported on the efficiency of percutaneous vertebroplasty (PVP) or kyphoplasty for whole thoracic and lumbar glucocorticosteroid-induced osteoporotic vertebral compression fractures. We report a case of a 67-year-old man with intractable pain caused by successional VCFs treated by PVP.
Aged
;
Arthritis, Rheumatoid/drug therapy
;
Fractures, Compression/*radiography
;
Glucocorticoids/*adverse effects/therapeutic use
;
Humans
;
Kyphoplasty
;
Lumbar Vertebrae/radiography/surgery
;
Male
;
Osteoporosis/*chemically induced/radiography/surgery
;
Pulmonary Fibrosis/drug therapy
;
Thoracic Vertebrae/radiography/surgery
;
Vertebroplasty
6.Effects of curcumin on pain threshold and on the expression of nuclear factor κ B and CX3C receptor 1 after sciatic nerve chronic constrictive injury in rats.
Hong CAO ; Jin-Wei ZHENG ; Jia-Jia LI ; Bo MENG ; Jun LI ; Ren-Shan GE
Chinese journal of integrative medicine 2014;20(11):850-856
OBJECTIVETo investigate the effects of curcumin on pain threshold and the expressions of nuclear factor κ B (NF-κ B) and CX3C chemokine receptor 1 (CX3CR1) in spinal cord and dorsal root ganglion (DRG) of the rats with sciatic nerve chronic constrictive injury.
METHODSOne hundred and twenty male Sprague Dawley rats, weighing 220-250 g, were randomly divided into 4 groups. Sham surgery (sham) group: the sciatic nerves of rats were only made apart but not ligated; chronic constrictive injury (CCI) group: the sciatic nerves of rats were only ligated without any drug treatment; curcumin treated injury (Cur) model group: the rats were administrated with curcumin 100 mg/(kg·d) by intraperitoneal injection for 14 days after CCI; solvent control (SC) group: the rats were administrated with the solvent at the same dose for 14 days after CCI. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of rats were respectively measured on pre-operative day 2 and postoperative day 1, 3, 5, 7, 10 and 14. The lumbar segment L4-5 of the spinal cord and the L4, L5 DRG was removed at post-operative day 3, 7 and 14. The change of nuclear factor κ B (NF-κ B) p65 expression was detected by Western blotting while the expression of CX3CR1 was determined by immunohistochemical staining.
RESULTSCompared with the sham group, the TWL and MWT of rats in the CCI group were significantly decreased on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI, and the expressions of NF-κ B p65 and CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In the Cur group, the TWL of rats were significantly increased than those in the CCI group on post-operative day 7, 10 and 14 (P<0.05) and MWT increased than those in the CCI group on post-operative day 10 and 14 (P<0.05). In addition, the administration of curcumin significantly decreased the positive expressions of NF-κ B p65 and CX3CR1 in spinal cord and DRG (P<0.05).
CONCLUSIONOur study suggests that curcumin could ameliorate the CCI-induced neuropathic pain, probably through inhibiting CX3CR1 expression by the activation of NF-κ B p65 in spinal cord and DRG.
Animals ; Blotting, Western ; CX3C Chemokine Receptor 1 ; Curcumin ; pharmacology ; Ganglia, Spinal ; metabolism ; Lumbar Vertebrae ; NF-kappa B ; metabolism ; Pain Threshold ; drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytokine ; metabolism ; Receptors, HIV ; metabolism ; Sciatic Nerve ; injuries ; metabolism ; Spinal Cord ; metabolism
7.Preliminary curative effect of interspinous blocking injection guiding by X-ray for the diagnosis and treatment of lumbar Baastrup's disease.
Kan LIU ; Wen-Wen WU ; Ji-Dong GUO ; Dong-Feng REN ; Li LI ; Hua-Dong WANG ; Jia TANG
China Journal of Orthopaedics and Traumatology 2014;27(3):220-223
OBJECTIVETo evaluate the preliminary curative effect of interspinous injections for the diagnosis and treatment of back pain caused by lumbar kissing spine (Baastrup's disease) under fluoroscopically guiding.
METHODSFrom November 2011 to March 2013,17 patients with back pain caused by Baastrup's disease were treated with fluoroscopically-guided interspinous injections, including 7 males and 10 females with an average age of 49.6 years old ranging from 40 to 71 years old; the duration of the disease ranged from 2 to 5 years with a mean of 3.7 years. The visual analogue scale (VAS) and the lumbar segments range of motion (ROM) was analyzed at pre-operation, 2 days, 3 months and final followed-up after operation, the effects were evaluated with modified Macnab standard.
RESULTSAll patients were follow-up from 6 to 10 months with an average of 7.6 months. The pre-operative VAS was 6.41 +/- 0.94, the postoperative VAS at different time points improved significantly comparing with pre-operation,and the differences were statistically significant (P < 0.01). There was no significant difference in VAS at different time points after operation (P > 0.05). The ROM of operated segment and adjacent segment was (4.88 +/- 0.86) degrees and (6.82 +/- 0.73) degrees respectively at pre-operation. The postoperative operated segment ROM at different time points improved significantly comparing with pre-operation, and the differences were statistically significant (P < 0.05). Compared with pre-operation, there was no significant difference in adjacent segment ROM at different time points after operation (P > 0.05). According to modified Macnab, the result was excellent in 6 cases, good in 7 cases, fair in 3 cases and poor in 1 case.
CONCLUSIONFluoroscopically-guided interspinous injections is an effective method for the diagnosis and treatment of Baastrup's disease. The method has advantages of simple operation, minimal invasion and safety, satisfactory short-term and medium-term therapeutic effect; it can also effectively lessen the pain of lumbar and back.
Adult ; Aged ; Anesthetics, Local ; administration & dosage ; Female ; Humans ; Low Back Pain ; diagnosis ; diagnostic imaging ; drug therapy ; Lumbar Vertebrae ; diagnostic imaging ; drug effects ; Male ; Middle Aged ; Nerve Block ; Spinal Diseases ; diagnosis ; diagnostic imaging ; drug therapy ; Tomography, X-Ray Computed
8.A Case of Epidural Abscess Occurred after Liver Abscess Complicated by Transarterial Chemoembolization in a Patient with Metastatic Cancer to Liver.
Yong Jae LEE ; Gwang Ha KIM ; Do Youn PARK ; Suk KIM ; Chang Jun PARK ; Tae Kyun KIM ; Jung Hee KOH
The Korean Journal of Gastroenterology 2013;61(4):225-229
Transarterial chemoembolization (TACE) is one of the most effective therapies for unresectable hepatocelluar carcinoma or metastatic hypervascular tumors. Abscess occurring in the other organs beside the liver after TACE is a complication that often occurs, sometimes potentially fatal. We report a case of spinal epidural abscess occurred after liver abscess complicated by TACE in a patient with metastatic neuroendocrine tumors to the liver. A 67-year-old female underwent TACE first for the metastatic lesions to liver, with a history of pancreatoduodenectomy for the primary pancreatic neuroendocrine tumor. Four days after TACE, sudden high fever occurred, and liver abscess was found on abdominal CT. Two days later, back pain and radiating pain to the right leg occurred, and lumbar spine MRI showed spinal epidural abscess. After intravenous antibiotics for 8 weeks and partial laminectomy, the patient recovered and was discharged without complications.
Aged
;
Anti-Bacterial Agents/therapeutic use
;
Carcinoma, Hepatocellular/secondary/*therapy
;
Chemoembolization, Therapeutic/*adverse effects
;
Epidural Abscess/*etiology/microbiology/surgery
;
Escherichia coli/isolation & purification
;
Escherichia coli Infections/drug therapy
;
Female
;
Humans
;
Laminectomy
;
Liver Abscess/*etiology
;
Liver Neoplasms/secondary/*therapy
;
Lumbar Vertebrae/microbiology/radiography
;
Magnetic Resonance Imaging
;
Neuroendocrine Tumors/pathology/surgery
;
Pancreaticoduodenectomy
;
Tomography, X-Ray Computed
9.Anterior herniation of lumbar disc induces persistent visceral pain: discogenic visceral pain: discogenic visceral pain.
Yuan-Zhang TANG ; Moore-Langston SHANNON ; Guang-Hui LAI ; Xuan-Ying LI ; Na LI ; Jia-Xiang NI
Chinese Medical Journal 2013;126(24):4691-4695
BACKGROUNDVisceral pain is a common cause for seeking medical attention. Afferent fibers innervating viscera project to the central nervous system via sympathetic nerves. The lumbar sympathetic nerve trunk lies in front of the lumbar spine. Thus, it is possible for patients to suffer visceral pain originating from sympathetic nerve irritation induced by anterior herniation of the lumbar disc. This study aimed to evaluate lumbar discogenic visceral pain and its treatment.
METHODSTwelve consecutive patients with a median age of 56.4 years were enrolled for investigation between June 2012 and December 2012. These patients suffered from long-term abdominal pain unresponsive to current treatment options. Apart from obvious anterior herniation of the lumbar discs and high signal intensity anterior to the herniated disc on magnetic resonance imaging, no significant pathology was noted on gastroscopy, vascular ultrasound, or abdominal computed tomography (CT). To prove that their visceral pain originated from the anteriorly protruding disc, we evaluated whether pain was relieved by sympathetic block at the level of the anteriorly protruding disc. If the block was effective, CT-guided continuous lumbar sympathetic nerve block was finally performed.
RESULTSAll patients were positive for pain relief by sympathetic block. Furthermore, the average Visual Analog Scale of visceral pain significantly improved after treatment in all patients (P < 0.05). Up to 11/12 patients had satisfactory pain relief at 1 week after discharge, 8/12 at 4 weeks, 7/12 at 8 weeks, 6/12 at 12 weeks, and 5/12 at 24 weeks.
CONCLUSIONSIt is important to consider the possibility of discogenic visceral pain secondary to anterior herniation of the lumbar disc when forming a differential diagnosis for seemingly idiopathic abdominal pain. Continuous lumbar sympathetic nerve block is an effective and safe therapy for patients with discogenic visceral pain.
Adult ; Aged ; Female ; Humans ; Intervertebral Disc ; drug effects ; pathology ; physiopathology ; Intervertebral Disc Displacement ; complications ; physiopathology ; Low Back Pain ; drug therapy ; Lumbar Vertebrae ; drug effects ; pathology ; physiopathology ; Lumbosacral Region ; Male ; Middle Aged ; Prospective Studies ; Visceral Pain ; drug therapy ; Young Adult
10.The Effect of Zoledronic Acid on the Volume of the Fusion-Mass in Lumbar Spinal Fusion.
Ye Soo PARK ; Hong Sik KIM ; Seung Wook BAEK ; Dong Yi KONG ; Jeong Ah RYU
Clinics in Orthopedic Surgery 2013;5(4):292-297
BACKGROUND: Few studies have explored the effects of bisphosphonates on bony healing in patients undergoing spinal fusion surgery. Most previous studies used animal models and found that bisphosphonate shows negative effects on spinal fusion consolidation. We intended to evaluate the effect of a single-dose of zoledronic acid on the volume of the fusion-mass in lumbar spinal fusion. METHODS: A retrospective review was carried out on 44 patients with symptomatic degenerative lumbar spinal stenosis who underwent one or two-level posterolateral fusion from January 2008 and January 2011. They were divided into 4 groups: group 1, autograft and zoledronic acid; group 2, allograft and zoledronic acid; group 3, autograft alone; and group 4, allograft alone. Functional radiography and three-dimensional computed tomography scans were used to evaluate and quantify the volume of the fusion-mass. The visual analog scale (VAS), the Oswestry disability index (ODI), and the short form 36 (SF-36) were used to evaluate the clinical outcomes. RESULTS: The mean volume of the fusion-mass per level was 8,814 mm3, 8,035 mm3, 8,383 mm3, and 7,550 mm3 in groups 1, 2, 3, and 4, respectively, but there were no significant differences between the groups (p = 0.829). There were no significant decreases in the volume of the fusion-mass (p = 0.533) in the zoledronic acid groups (groups 1 and 2). The VAS, the ODI, and the SF-36 at the 6-month follow-up after surgery were not significantly different (p > 0.05) among the 4 groups. The VAS, the ODI, and the SF-36 were not correlated with the volume of the fusion-mass (p = 0.120, 0.609, 0.642). CONCLUSIONS: A single dose of zoledronic acid does not decrease the volume of the fusion-mass in patients undergoing spinal fusion with osteoporosis. Therefore, we recommend that zoledronic acid may be used after spinal fusion in osteoporotic patients.
Aged
;
Aged, 80 and over
;
Bone Density Conservation Agents/*therapeutic use
;
Diphosphonates/*therapeutic use
;
Female
;
Humans
;
Imidazoles/*therapeutic use
;
Lumbar Vertebrae/drug effects/pathology/radiography/surgery
;
Male
;
Middle Aged
;
Osteoporosis/drug therapy
;
Pain Measurement
;
Pain, Postoperative
;
Quality of Life
;
Retrospective Studies
;
Spinal Fusion/adverse effects/*methods
;
Spinal Stenosis/pathology/radiography/*surgery
;
Treatment Outcome

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