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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: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. MATERIALS AND METHODS: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. RESULTS: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. CONCLUSION: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
Back Pain ; Bupivacaine* ; Diagnosis ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain* ; Magnetic Resonance Imaging ; Methods ; Spinal Fusion ; Spine

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy

STUDY DESIGN: Retrospective study. PURPOSE: To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. OVERVIEW OF LITERATURE: Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. METHODS: Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. RESULTS: No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). CONCLUSIONS: Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.
Anti-Inflammatory Agents, Non-Steroidal ; Diagnosis ; Drug Therapy ; Humans ; Incidence ; Low Back Pain* ; Retrospective Studies ; Spine ; Tramadol* ; Visual Analog Scale

STUDY DESIGN: Experimental animal study. PURPOSE: We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. OVERVIEW OF LITERATURE: The pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner. METHODS: The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups. RESULTS: There were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p <0.05). CONCLUSIONS: When a low dose of the TNF-α inhibitor (10 µg of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 µg and 1,000 µg) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner.
Animals ; Calcitonin Gene-Related Peptide ; Diagnosis-Related Groups ; Etanercept* ; Ganglia, Spinal ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Models, Animal ; Necrosis* ; Needles ; Neurons ; Rats* ; Tumor Necrosis Factor-alpha

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

PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
Animals ; Female ; Femur/*innervation/*metabolism ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/*metabolism

STUDY DESIGN: Observational study. PURPOSE: To assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD). OVERVIEW OF LITERATURE: Low back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial. METHODS: Using the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels. RESULTS: A gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002). CONCLUSIONS: These results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.
Dichlorodiphenyldichloroethane ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-6 ; Intervertebral Disc Degeneration* ; Intervertebral Disc* ; Leg ; Low Back Pain ; Magnetic Resonance Imaging ; Nerve Growth Factor ; Observational Study ; Tumor Necrosis Factor-alpha

STUDY DESIGN: Prospective study. PURPOSE: To examine the long-term effects of interspinous ligament injections of local anesthetics and steroids for the treatment of Baastrup's diseases. OVERVIEW OF LITERATURE: Baastrup's disease is associated with axial low back pains. Baastrup's disease has been more recently described as the "kissing spinous processes" disease. Several authors have reported methods for the diagnosis and treatment of the disease. However, there has been only one report of patients receiving interspinous ligament injections of agents for the treatment of Baastrup's disease. METHODS: Seventeen patients showed severe low back pains between spinous processes at L3-L4 or L4-L5. X-ray imaging, computed tomography, and magnetic resonance imaging revealed kissing spinous processes, consolidation of spinous process, or inflammation of an interspinous ligament. Pain reliefs after lidocaine and dexamethasone administration into interspinous ligament as therapy for low back pains were being examined and followed up. RESULTS: Low back pain scores significantly improved immediately after injection of the agents into interspinous ligaments. At final follow-up (1.4 year), low back pain scores significantly improved as compared with before the treatment. CONCLUSIONS: Findings from the current study indicate that lidocaine and dexamethasone administration into interspinous ligament in patients diagnosed with Baastrup's disease is effective for managing the pain associated with this disease.
Anesthetics, Local ; Dexamethasone ; Diagnosis ; Follow-Up Studies ; Humans ; Inflammation ; Lidocaine* ; Ligaments* ; Low Back Pain ; Magnetic Resonance Imaging ; Prospective Studies ; Steroids