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STUDY DESIGN: Retrospective study. PURPOSE: We conducted a study to investigate the time course changes in bone metabolic markers after the administration of the anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody and to assess drug compliance among osteoporotic patients. OVERVIEW OF LITERATURE: The anti-RANKL antibody is expected to provide an improvement in those with a bone metabolism disorder. However there are only a few clinical reports available on the effect of treatment. METHODS: We included 40 post-menopausal osteoporotic patients who received the anti-RANKL antibody. To determine the time course changes in the bone metabolic markers, we measured the serum tartrate-resistant acid phosphatase 5b (TRACP 5b; a bone resorption marker) and the serum N-terminal propeptide of type 1 collagen (P1NP; a bone formation marker) levels prior to and 1 month after administrating the anti-RANKL antibody. To evaluable drug compliance, we assessed the dropout rate during treatment and at 6 months after treatment. RESULTS: The average TRACP 5b level significantly decreased from 574.8 mU/dL before treatment to 153.2 mU/dL 1 month after treatment (p<0.05). There was no significant difference in the average P1NP level, which was 56.9 microG/L and 35.1 microG/L before and 1 month after treatment, respectively (p>0.05). As for drug compliance, we did not have any dropouts during the treatment or after 6 months (dropout rate: 0%). CONCLUSIONS: Our study suggests that anti-RANKL antibody treatment suppresses bone resorption and maintains bone formation.
Acid Phosphatase ; Bone Resorption ; Collagen Type I ; Compliance* ; Humans ; Metabolism ; Osteogenesis ; Osteoporosis* ; Patient Dropouts ; RANK Ligand ; Retrospective Studies

PURPOSE: Sacroiliac fixation using iliac screws for highly unstable lumbar spine has been reported with an improved fusion rate and clinical results. On the other hand, there is a potential for clinical problems related to iliac fixation, including late sacroiliac joint arthritis and pain. MATERIALS AND METHODS: Twenty patients were evaluated. Degenerative scoliosis was diagnosed in 7 patients, failed back syndrome in 6 patients, destructive spondyloarthropathy in 4 patients, and Charcot spine in 3 patients. All patients underwent posterolateral fusion surgery incorporating lumbar, S1 and iliac screws. We evaluated the pain scores, bone union, and degeneration of sacroiliac joints by X-ray imaging and computed tomography before and 3 years after surgery. For evaluation of low back and buttock pain from sacroiliac joints 3 years after surgery, lidocaine was administered in order to examine pain relief thereafter. RESULTS: Pain scores significantly improved after surgery. All patients showed bone union at final follow-up. Degeneration of sacroiliac joints was not seen in the 20 patients 3 years after surgery. Patients showed slight low back and buttock pain 3 years after surgery. However, not all patients showed relief of the low back and buttock pain after injection of lidocaine into the sacroiliac joint, indicating that their pain did not originate from sacroiliac joints. CONCLUSION: The fusion rate and clinical results were excellent. Also, degeneration and pain from sacroiliac joints were not seen within 3 years after surgery. We recommend sacroiliac fixation using iliac screws for highly unstable lumbar spine.
Aged ; Arthritis/*surgery ; Bone Screws ; Female ; Humans ; Low Back Pain/diagnosis/epidemiology ; Lumbar Vertebrae/*surgery ; Male ; Middle Aged ; Pain/diagnosis/*epidemiology ; Sacroiliac Joint/*immunology/*pathology

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats. METHODS: Mechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry. RESULTS: Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01). CONCLUSIONS: The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.
Animals ; Cytokines ; Diagnosis-Related Groups ; Ganglia, Spinal* ; Hyperalgesia ; Immunohistochemistry ; Negotiating ; Neurons ; NF-kappa B ; RANK Ligand* ; Rats* ; Sciatic Nerve* ; Up-Regulation

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. METHODS: The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. RESULTS: Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). CONCLUSIONS: Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
Animals ; Antibodies ; Astrocytes ; Calcium ; Cytokines ; Ganglia, Spinal ; Horns ; Hyperalgesia ; Inflammation ; Microglia ; Neuroglia ; Prostaglandins ; Rats* ; Sciatic Nerve* ; Spinal Cord* ; Surgical Instruments ; Up-Regulation*

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

STUDY DESIGN: Retrospective, observational, single-center study. PURPOSE: To investigate the long-term outcomes of in situ fusion procedures for treating dysplastic spondylolisthesis. OVERVIEW OF LITERATURE: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications. METHODS: In total, 12 of 28 patients who underwent in situ fusion for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974 to 2004 were followed up in August 2013. Surgical complications were evaluated. Low back pain and leg pain were assessed using a visual analog scale (VAS). Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle measurement on radiographic images (profile view in the neutral standing position), was evaluated during preoperative, postoperative, and final examinations. RESULTS: The mean follow-up duration, patient age at the final examination, and patient age at operation were 20.0±7.2, 42.3±13.3, and 22.3±11.4 years, respectively. No complications were reported. Mean VAS scores for low back pain and leg pain were significantly lower at the final examination than at the preoperative examination (p<0.05). At the preoperative, postoperative, and final examinations, the mean lumbosacral angle was 32.3°±14.2°, 33.7°±11.8°, and 36.5°±16.4°, while the mean lumbar lordosis angle was 51.0°±14.8°, 48.6°±18.8°, and 49.6°±15.5°, respectively. No significant differences were noted among these values across the different time periods (p<0.05). CONCLUSIONS: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications such as nerve paralysis that may occur after repositioning operation and maintains appropriate long-term sagittal alignment, even 20 years after operation.
Animals ; Follow-Up Studies ; Humans ; Leg ; Lordosis ; Low Back Pain ; Paralysis ; Retrospective Studies ; Spondylolisthesis* ; Visual Analog Scale

STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. METHODS: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. RESULTS: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). CONCLUSIONS: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.
Animals ; Back Pain ; Calcitonin Gene-Related Peptide ; Cytokines ; Diagnosis-Related Groups ; Endothelial Growth Factors ; Ganglia ; Ganglia, Spinal* ; Humans ; Intervertebral Disc* ; Low Back Pain ; Models, Animal ; Needles ; Neuropeptides* ; Punctures ; Rats* ; Rats, Sprague-Dawley ; Sodium ; Sodium Chloride ; Spinal Nerve Roots* ; Vascular Endothelial Growth Factor A*

STUDY DESIGN: Animal model study. PURPOSE: The purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin gene-related peptide in rats over time. OVERVIEW OF LITERATURE: Vertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve. METHODS: We used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed. RESULTS: H&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period. CONCLUSIONS: These results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury.
Animals ; Atrophy ; Back Muscles* ; Calcitonin Gene-Related Peptide ; Cicatrix ; Eosine Yellowish-(YS) ; Ganglia, Sensory ; Ganglia, Spinal ; Granulation Tissue ; Hematoxylin ; Humans ; Male ; Models, Animal ; Muscular Atrophy ; Myalgia ; Rats* ; Rats, Sprague-Dawley ; Spine

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Aged ; Aged, 80 and over ; Drug Therapy, Combination/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Thiazines/administration & dosage/adverse effects/*therapeutic use ; Thiazoles/administration & dosage/adverse effects/*therapeutic use ; gamma-Aminobutyric Acid/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use