山内 かづ代

BACKGROUND: Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic low back pain. We conducted a prospective cohort study to evaluate the efficacy and safety of intradiscal injection of the interleukin-6 receptor antibody tocilizumab in patients with discogenic low back pain. METHODS: Thirty-two consecutive patients were intradiscally injected with 2 mL of 0.5% bupivacaine (control group). Another 31 consecutive patients were intradiscally injected with 40 mg tocilizumab and 1-2 mL of 0.5% bupivacaine (tocilizumab group) at the same time. Prior to treatment, the vertebral origin of low back pain was confirmed in all patients based on pain provocation during discography and pain relief with 1 mL of 1% xylocaine. Numeric rating scale and Oswestry disability index scores were used to evaluate pain level before and after treatment between the 2 groups. The association between pain relief with tocilizumab and intervertebral disc degeneration grade was also determined. RESULTS: At the end of the study (8 weeks after treatment), 30 patients in each group were evaluable. In the tocilizumab group, numeric rating scale and Oswestry disability index scores improved significantly at 2 and 4 weeks after treatment, respectively. Intervertebral disc degeneration was not associated with improvement of numeric rating scale score in the tocilizumab group. Local infection (i.e., discitis) was observed in 1 patient in the tocilizumab group. CONCLUSIONS: The results demonstrate the clinical relevance of interleukin-6 in discogenic low back pain. Intradiscal tocilizumab injection was shown to exert a short-term analgesic effect in patients with discogenic low back pain. Further research is required to determine the long-term effects of intradiscal tocilizumab therapy in patients with discogenic low back pain.

We investigated the efficacy of pregabalin (PGB) for neuropathic leg pain in lumbar spinal stenosis (LSS) patients with disturbed activities of daily living (ADL)/quality of life (QOL) in a prospective observational study. Subjects were a total of 104 LSS patients with neuropathic pain (NeP) in leg and neurological intermittent claudication (IMC) refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) for at least a month. NeP was identified using screening tool, Pain DETECT questionnaire. Visual analog scale (VAS) scores and responses to the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were assessed before and 6 weeks after PGB treatment initiation. Changes in IMC distance and adverse events were also recorded. PGB significantly improved their VAS scores for pain and sleep quality (P < 0.001). With respect to JOABPEQ, significant improvements were observed with regard to the following dimensions: pain-related disorders (P < 0.01), lumbar spine dysfunction (P = 0.031), gait disturbance (P = 0.028), and psychological disorders (P = 0.014). The IMC distance showed an improvement tendency after PGB treatment, albeit with no significance (P = 0.063). Minor adverse events such as dizziness were observed. PGB can be effective for neuropathic leg pain refractory to NSAIDs in LSS patients, resulting in not only pain control but also improving lower back pain-related ADL/QOL scores.

[This corrects the article on p. 338 in vol. 9, PMID: 26097648.].

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-caused pyogenic spondylitis is a serious complication associated with lumbar fusion surgery. Often, anti-MRSA drugs are not used properly or patients discontinue drug use because of side effects including renal failure. CASE PRESENTATION: We report a case at our hospital of a 54-year-old male renal-transplant patient who developed MRSA vertebral osteomyelitis after spinal fusion and was treated effectively with linezolid. After diagnosis of post-fusion surgery osteomyelitis, we conducted emergency flushing and debridement and began linezolid treatment (1200 mg/day, divided) immediately after the surgery. The level of C-reactive protein gradually decreased and became negative 4 weeks after the initiation of linezolid treatment. Serum creatinine level was approximately 1.3 mg/dL throughout the treatment period, indicating no deterioration in renal function. CONCLUSION: These results suggest that early flushing and debridement together with linezolid administration is an effective treatment for MRSA vertebral osteomyelitis in renal-transplant patients.

Recently several authors have reported that diffusion tensor imaging (DTI) might provide a new understanding of sciatica. The purpose of this study was to investigate the clinical feasibility of DTI for the evaluation of lumbar spinal nerve of patients with sciatica associated with lumbar degenerative disorders. Thirty-four patients (25men, mean age63. 3years) with degenerated lumbar disease, 14 patients with lumbar spinal stenosis with foraminal stenosis, 12 with lumbar spinal stenosis without foraminal stenosis, five with lumbar disc herniation, two with discogenic low back pain, and one with spondylolysis who underwent 3.0T magnetic resonance (MR) imaging and surgical treatment were included in the present study. Fractional anisotropy (FA) was calculated from an FA map, and tractography was investigated. In asymptomatic nerves, tractography showed all L3-S1 spinal nerve roots clearly. Abnormalities of tractography were classified into three types by shape; "Disrupted", "Narrowing", and "Tapering". More abnormalities of tractography were found in patients with lumbar spinal stenosis, and especially in patients with foraminal stenosis. The disrupted type was the most common. The mean FA of entrapped symptomatic nerves was less than seen on the intact side. This study demonstrates that tractography shows abnormal findings for nerve roots in lumbar spinal degeneration and that FA decreases in symptomatic roots. DTI may offer not only morphological evaluation, but also quantitative evaluation. We believe that DTI can be used as a tool for the diagnosis of lumbar spinal degenerative disease.

The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain-related mediators, such as interleukin-6 (IL-6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL-6 and IL-6 receptor (IL-6R) expression after IVD injury as well as determine the involvement of IL-6/IL-6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL-6 and IL-6R in IVDs by enzyme-linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL-6 inhibitor by evaluating pain-related protein, calcitonin gene-related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL-6 and IL-6R. IL-6 and IL-6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL-6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL-6 and IL-6R expression levels are responsive to IVD injury and that inhibition of IL-6/IL-6R signaling may be a promising analgesic treatment for degenerative disc diseases.

PURPOSE: To investigate the effect of intraperitoneal administration of an anti-p75 neurotrophin receptor (p75NTR) antibody on reducing neuropathic pain in a rat model of brachial plexus avulsion (BPA). METHODS: We randomly assigned 40 male Wistar rats to 4 groups. In the BPA group, the C8-T1 roots were avulsed from the spinal cord at the lower trunk level, and saline was administered intraperitoneally. In the anti-p75NTR groups, 1 μL or 50 μL anti-p75NTR antibody was administered intraperitoneally after avulsion. In the sham-operated group, the lower trunk level was exposed, and saline was administered intraperitoneally. Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments and CatWalk gait analysis at various time points until 15 days after administration. At 3 and 15 days after administration, sensory neurons involved in pain perception and satellite glial cells in the ipsilateral C7 dorsal root ganglia were immunolabeled with antibodies against calcitonin gene-related peptide and glial fibrillary acidic protein (GFAP), respectively. At both time points, microglial and astrocyte activation, indicative of spinal pain transmission, were immunohistochemically examined in the ipsilateral dorsal horn of the spinal cord (C7) using anti-ionized calcium-binding adaptor molecule 1 and anti-GFAP antibodies, respectively. RESULTS: The gait pattern was significantly improved in both anti-p75NTR groups compared with the BPA group. There were significantly fewer calcitonin gene-related peptide-immunoreactive (IR) neurons, neurons encircled by GFAP-IR satellite glial cells, and GFAP-IR astrocytes in both anti-p75NTR groups compared with the BPA group at both time points. Fewer ionized calcium-binding adaptor molecule 1-IR microglia were quantified in both anti-p75NTR groups compared with the BPA group, but this was only significant at 15 days after administration. CONCLUSIONS: Systemic application of the p75NTR inhibitory antibody suppressed neuropathic pain after BPA. CLINICAL RELEVANCE: p75NTR may be a potential therapeutic target for the clinical treatment of neuropathic pain in BPA injury.

椎間板性腰痛の病態と今後の展望について、1)innervation:感覚神経支配が存在すること、2)inflammation:その感覚神経を感作する因子が存在すること、3)hypermobility:不安定性があること、に分けて述べた。現時点では、術前の痛みや術後残存する痺れと術前拡散テンソル画像での障害の程度が相関しており、基礎、臨床的に認められた椎間板内への神経発芽を可視化することが現実化できると期待される。

PURPOSE: Nuclear factor-κB (NF-κB), receptor activator of NF-κB (RANK), and RANK ligand (RANKL) are transcriptional regulators of inflammatory cytokines. RANKL expression in dorsal root ganglion (DRG) neurons is elevated in animal models of pain or intervertebral disc herniation. We sought to evaluate the effect of anti-RANKL antibodies on sensory nerves innervating injured intervertebral discs. METHOD: We labeled DRG neurons innervating L5-6 discs with FluoroGold (FG). The L5-6 discs of 36 rats were punctured using a 23-gage needle and 18 rats underwent sham surgery without disc puncture. The puncture group was evenly subdivided into a group in which 10 μl saline was administered to the injured disc and a group in which 10 μl of anti-RANKL antibody was administered. Seven and 14 days postsurgery, DRGs at L2 level were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was determined. Amount of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was measured within the intervertebral discs in each group at 7 and 14 days after surgery using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The proportion of CGRP-IR DRG neurons to total FG-labeled neurons innervating injured intervertebral discs and amount of TNF-α and IL-6 in the injured discs in the saline control group was significantly increased compared with that found in rats from the sham surgery group (P < 0.05). However, application of anti-RANKL antibody to the injured discs significantly decreased the proportion of CGRP-IR DRG neurons to total FG-labeled neurons and amount of TNF-α and IL-6 in the injured discs (P < 0.05). CONCLUSIONS: TNF-α and IL-6 in the injured discs increased and CGRP expression increased in DRG neurons innervating injured discs, and antibodies to RANKL could suppress this increased TNF-α, IL-6, and CGRP expression. RANKL may be a therapeutic target for pain control in patients with lumbar disc degeneration.

PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-α (TNFα) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFα inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFα is one factor that induces OA pain.

STUDY DESIGN: Prospective case series. PURPOSE: To examine the clinical efficacy of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion (OLIF) for degenerated lumbar spinal kyphoscoliosis. OVERVIEW OF LITERATURE: The existing surgical procedures for the treatment of spinal kyphotic deformity, including Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection procedures, are invasive in nature. Extreme lateral interbody fusion to provide less invasive treatment of the deformity has been reported, but complications including spinal nerve and psoas muscle injury have been noted. In the current study, we examined the clinical efficacy and complications of OLIF for degenerated lumbar spinal kyphoscoliosis. METHODS: Twelve patients with degenerated lumbar spinal kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with open pedicle screws or percutaneous pedicle screws, without real-time monitoring by electromyography. Visual analog scale score and Oswestry disability index were evaluated before and 12 months after surgery, and fusion rate at OLIF cage, correction of the deformity, total blood loss, and surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery (p<0.05). Fusion rate was found to be 90%, balance parameters also improved after surgery (p<0.05), and average total blood loss was less than 350 mL. There was no spinal nerve, major vessel, peritoneal, or urinary injury, or breakage of instrumentation. CONCLUSIONS: OLIF surgery for degenerated lumbar spinal kyphoscoliosis is less invasive than other procedures and good surgical results were produced without major complications.

STUDY DESIGN: Retrospective case series. PURPOSE: To examine the most effective duration of teriparatide use for spinal fusion in women with postmenopausal osteoporosis. OVERVIEW OF LITERATURE: We reported that daily subcutaneous injection of teriparatide (parathyroid hormone) significantly improved bone union after instrumented lumbar posterolateral fusion (PLF) in women with postmenopausal osteoporosis when compared with oral administration of bisphosphonate. However, the most effective duration of teriparatide use for spinal fusion has not been explored. METHODS: Forty-five women with osteoporosis diagnosed with degenerative spondylolisthesis from one of the three treatment groups were evaluated based on: short-duration treatment (average, 5.5 months; n=15; daily subcutaneous injection of 20 µg teriparatide), long-duration treatment (average, 13.0 months; n=15; daily subcutaneous injection of 20 µg teriparatide), and bisphosphonate treatment (average, 13.0 months; n=15; weekly oral administration of 17.5 mg risedronate). All patients underwent PLF with a local bone graft. Fusion rate and duration of bone union were evaluated 1.5 years after surgery. RESULTS: Bone union rate and average duration for bone union were 92% and 7.5 months in the long-duration treatment group, 80% and 8.5 months in the short-duration treatment group, and 70% and 10.0 months in the bisphosphonate treatment group, respectively. Results of bone union rate and average duration for bone union in the teriparatide treatment groups were significantly superior to those in the bisphosphonate treatment group (p<0.05); whereas, significantly superior results were observed in long-duration treatment group when compared with short-duration treatment group (p<0.05). CONCLUSIONS: Daily injection of teriparatide for bone union was more effective than oral administration of bisphosphonate. Furthermore, a longer period of teriparatide treatment for bone union was more effective than a shorter period of same treatment.

This study aimed to evaluate the time course of local changes during the acute phase of gastrocnemius muscle strain, in a rat model, using an in vivo imaging system. Thirty-eight, 8-week-old Sprague-Dawley male rats were used in our study. Experimental injury of the right gastrocnemius muscle was achieved using the drop-mass method. After inducing muscle injury, a liposomally formulated indocyanine green derivative (LP-iDOPE, 7 mg/kg) was injected intraperitoneally. We evaluated the muscle injuries using in vivo imaging, histological examinations, and enzyme-linked immunosorbent assays. The fluorescence peaked approximately 18 h after the injury, and decreased thereafter. Histological examinations revealed that repair of the injured tissue occurred between 18 and 24 h after injury. Quantitative analyses for various cytokines demonstrated significant elevations of interleukin-6 and tumor necrosis factor-α at 3 and 18 h post-injury, respectively. The time course of fluorescence intensity, measured using in vivo imaging, demonstrated that the changes in cytokine levels and histopathologic characteristics were consistent. Specifically, these changes reached peaked 18 h post-injury, followed by trends toward recovery.

PURPOSE: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. MATERIALS AND METHODS: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. CONCLUSION: OLIF surgery produced good surgical results without any major complication.

An 80-year-old woman presented with severe thoracolumbar kyphosis due to spinal tuberculosis with chronic low back pain and gait disturbance. Radiographs showed T9-L1 bony union in the anterior and posterior longitudinal ligaments. Rigid bony union of the L2 and L3 vertebral bodies, with trapezoid-shaped deformity, a sagittal vertical axis (SVA) of approximately 570 mm, and a severe pelvic posterior inclination, were also evident. No residual tuberculous disease was detected. The patient was treated with kyphoplasty, which included an L2 pedicle subtraction vertebral osteotomy (PSO), and T9-S1 fixation. The procedure yielded a 45° correction in the sagittal alignment and enhanced local stability, resulting in an SVA of 50 mm. Her post-operative lower back pain and the gait disturbance resolved. The osteotomy site showed sufficient bony union 8 months post-operatively. PSO yielded marked improvements and stability with no complications such as pseudoarthritis at the osteotomy site. Also her sagittal alignment was corrected to achieve adequate stability with sufficient activities of daily living and improved quality of life. Vertebral osteotomy on those with rigid deformity gives good and stable clinical outcome.

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 µG/L and 35.1 µG/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.

BACKGROUND: Muscle injury is common and is thought to account for 10%-50% of all sports-related injuries. The use of rest, ice, compression, and elevation is common in clinical practice, but many treatments over a long period are required to produce a therapeutic effect. We evaluated the utility of photodynamic therapy as a new treatment option for the acute stage of muscle injury. METHODS: Twenty 8-week-old Sprague-Dawley male rats underwent experimental injury of the right gastrocnemius muscle with a drop-mass method. After muscle injury was induced, a liposomally formulated indocyanine green derivative (7 mg/kg) near-infrared laser irradiation was performed at 18 h after injury. Local time-dependent changes in the treatment (n = 14) and no treatment (n = 14) groups were evaluated with in vivo imaging, histologic examination, and enzyme-linked immunosorbent assay methods. RESULTS: In vivo imaging fluorescence values were significantly higher in the no treatment group, whereas interleukin-6 and tumor necrosis factor-α levels were significantly higher in the treatment group at 18 h after injury. Histologic examination results revealed that the treatment group had less bleeding and more degeneration repair processes than the no treatment group at 24 h and 1 week after muscle injury. CONCLUSIONS: These findings suggest that photodynamic therapy promotes a tissue-repairing effect during the early stage of muscle injury.

BACKGROUND: Corrective surgery for kyphoscoliosis patients tend to be highly invasive due to osteotomy. The present case introduce less invasive corrective surgery using anterior oblique lateral interbody fusion (OLIF) technique. CASE PRESENTATION: An 80-year-old Japanese man with a history of Parkinson's disease presented to our hospital because of severe kyphoscoliosis and gait disturbance. Considering the postsurgical complications due to osteotomy, we performed an anterior-posterior combined corrective fusion surgery: OLIF of Lumbar (L) 2-3, L3-4, and L4-5 (Medtronic Sofamor Danek, Memphis, TN, USA) followed by L5-Sacral (S) 1 anterior lumbar fusion via the OLIF approach using an anterior intervertebral cage, and posterior L3-4 and L4-5 facetectomy and posterior fusion using percutaneous pedicle screws from Thoracic (T) 10 to S1 with a T-9 hook system. The surgery was performed in a less invasive manner with no osteotomy, and it improved the sagittal alignments with moderate restoration, which improved the patient's posture and gait disturbance. The patient showed transient muscle weakness of proximal lower extremity contralateral side to the surgical site, which fully recovered by physical rehabilitation 3 months after the surgery. CONCLUSION: The surgical corrective procedure using the minimally invasive OLIF method including L5-S1 fusion showed a great advantage in treating degenerative kyphoscoliosis in a Parkinson's disease patient in its less-invasive approac.

脊椎疾患に伴う跛行で最も頻度が高いのが様々な要因による脊柱管狭窄症である。特に腰部脊柱管狭窄の認識は歴史的にはVerbiestが1949年に仏語で3例、そして1954年に英語で7例を報告したことに始まるとされている。我が国では若松が1970年に初めて本症の13例を考察し報告した。やがて1976年にArnoldiらが国際的な会議を経て国際分類を著した頃から、急速に疾患認識が高まったといえる。臨床症状として、(1)臀部から下肢の疼痛やしびれを有する、(2)臀部から下肢の疼痛やしびれは立位や歩行の持続によって出現あるいは増悪し、前屈や座位保持で軽快する、(3)MRIなどの画像で脊柱管の変性狭窄状態が確認され、臨床所見を説明できると考えられている。本稿では病態、診断、治療、鑑別診断について述べたい。(著者抄録)

BACKGROUND: Low back pain (LBP) is a major public health problem and the most common cause of workers' disability, resulting in substantial economic burden in terms of workers' compensation and medical costs. Sitting is a recognized potential risk factor for developing LBP. Therefore, eliminating risk factors associated with working conditions and individual work capacity may be beneficial in preventing LBP in sitting workers. The purpose of this prospective cross-sectional study is to investigate the prevalence of LBP and examine risk factors that contribute to the development of LBP in sitting workers at an electronics manufacturing company. METHODS: A cross-sectional survey was administered to all subjects to assess the prevalence of LBP persisting for at least 48 h during the recent week. Data on demographic characteristics and potential risk factors for LBP were collected at routine annual check-ups. Patients with LBP completed the Roland-Morris Disability Questionnaire (RDQ), which provided information on the attributes of LBP. Univariate and multivariate regression analyses examined the association between LBP and potential risk factors. RESULTS: Of the 1,329 sitting workers, 201 (15.1 %) acknowledged experiencing LBP during the recent week. In female workers, weight and body mass index were significantly correlated with the RDQ score. Univariate analyses identified male sex, prior history of LBP, height ≥170 cm, and weight ≥70 kg as significant risk factors of LBP. Multivariate logistic regression analyses identified prior history of LBP and past history of lumbar spine surgery as significant risk factors of LBP. CONCLUSIONS: This study characterized the prevalence and attributes of LBP in Japanese sitting workers and provided information about potential risk factors contributing to occurrence of LBP in the workplace.

OBJECTIVES: To determine the direct effects of intra-articular injection of nerve growth factor (NGF) into normal rat hips and the time course of pain-related mediator appearance. METHODS: Using 36 numbers of 8-week-old male Sprague-Dawley rats, 30 μl of 1% Fluoro-Gold solution (FG) (Sham-operated group; n = 12), 30 μl of 1% FG with 50 μg/ml NGF (NGF50 group; n = 12), and 30 μl of 1% FG with 100 μg/ml NGF (NGF100 group; n = 12) were injected into the left hip joints. Neurons in the dorsal root ganglion (DRG) labeled with FG, and FG and calcitonin gene-related peptide-immunoreactivity (CGRP-IR) were counted. The synovia in the left hip joint was examined histologically. RESULTS: The NGF50 and NGF100 groups showed evidence of synovitis without cartilage degeneration compared with the Sham-operated group. At 7 days, the proportions of CGRP-IR FG-labeled to total FG-labeled neurons were 12%, 18%, and 36% in the Sham-operated, NGF50, and NGF100 groups, respectively. At 14 days, the proportions were 13%, 22%, and 35% in the Sham-operated, NGF50, and NGF100 groups, respectively. At 7 and 14 days, the NGF50 and NGF100 groups showed a significantly higher proportion of CGRP-IR FG-labeled neurons than the Sham-operated group. CONCLUSIONS: Intra-articular administration of NGF into the hip joint produces a novel rat model for hip pain.

Cerebellar hemorrhage remote from the site of surgery can complicate neurosurgical procedures. However, this complication after lumbar surgery is rare. Furthermore, hemorrhage in both the cerebellum and the temporal lobe after spine surgery is rarer still. Herein we present a case of remote hemorrhage in both the cerebellum and the temporal lobe after lumbar spine surgery. A 79-year-old woman with a Schwannoma at the L4 level presented with low back and bilateral leg pain refractory to conservative management. Surgery was undertaken to remove the Schwannoma and to perform posterior fusion. During the surgery, the dura mater was removed in order to excise the Schwannoma. Reconstruction of the dura mater was performed; postoperatively the patient had a cerebrospinal fluid leak. Five days after surgery, clouding of consciousness started gradually, and hemorrhage in the cerebellum and the temporal lobe was revealed by computed tomography. Emergent evacuation of the hemorrhage was performed and the patient recovered consciousness after the surgery. Leakage of cerebrospinal fluid may have induced this hemorrhage. While rare, intracranial hemorrhage after spine surgery can occur, sometimes requiring emergent intervention.

INTRODUCTION: Spinal cord stimulation (SCS) is sometimes preferable in some refractory chronic lower back pain (LBP) pathologies. SCS involves an insertion of electrode leads into the epidural space in the prone position under local anesthesia, followed by neurostimulator implantation under local/general anesthesia. These continuous procedures can cause transient post-operative LBP exacerbation and to make temporary pockets that will store redundant leads in it with some risk of subcutaneous irritation and infection in addition to making extra incisions. We introduce a modified simpler method for SCS implantation, systematically designed to be performed only under local anesthesia in a decubitus, non-prone position. MATERIALS AND METHODS: An 81-year-old patient with FBSS was treated. A physician was able to insert SCS leads with ease while the patient was in a decubitus position. The patient was comfortable, under totally local anesthesia, and the procedure produced no extra subcutaneous pockets. RESULT: The patient felt almost no LBP and reported no pain exacerbation during the operation. The SCS installation provided the patient with great improvement in both her lower back (NRS from 8 to 0-1) and leg (from 7 to 2) pain with a great improvement in her daily life activities. No adverse events were observed during the perioperative period. CONCLUSION: The modified SCS insertion method enabled us to achieve both intraoperative pain relief and complete SCS implantation in a minimally invasive manner.

BACKGROUND: The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model. METHODS: The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored. RESULTS: Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice. CONCLUSIONS: The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.

STUDY DESIGN: Case series. PURPOSE: To determine the utility of "PainVision" apparatus for the assessment of low back pain. OVERVIEW OF LITERATURE: A newly developed device, the PainVision PS-2100 (Nipro, Osaka, Japan), has been used to assess the perception of pain in a quantitative manner. In the current study, we aimed to evaluate the efficacy of PainVision for the assessment of low back pain. METHODS: We assessed 89 patients with low back pain. The numeric rating scale (NRS) score, McGill Pain Questionnaire (MPQ) score and the degree of pain calculated by PainVision were measured twice at 4-week intervals in each patient. An electrode was patched on the forearm surface of the patients and the degree of pain was automatically calculated (degree of pain=100×[current producing pain comparable with low back pain-current at perception threshold/current at perception threshold]). Correlations between NRS and MPQ scores and the degree of pain were determined using Spearman's rank correlation test. RESULTS: There was a strong correlation between the NRS and MPQ scores at each time point (rs =0.60, p<0.0001). The degree of pain also showed a moderate correlation with NRS and MPQ scores at each time point (rs =0.40, p<0.03). The change in the degree of pain over 4 weeks showed a moderate correlation with changes in the NRS and MPQ scores (rs =0.40, p<0.01). CONCLUSIONS: PainVision as self-reported questionnaires is a useful tool to assess low back pain.

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported. MATERIALS AND METHODS: TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating the femurs of Sprague Dawley rats were examined in control, sham, and ovariectomized (OVX) rats. We evaluated osteoporosis in the femurs and compared the proportion of TRPV1-ir DRG neurons innervating femur between the 3 groups of rats. RESULTS: OVX rats showed osteoporotic cancellous bone in the femur. FG labeled neurons were distributed from L1 to L6 DRG, but there was no significant difference in the proportion of labeled neurons between the 3 groups (p>0.05). The proportions of FG labeled TRPV1-ir DRG neurons were 1.7%, 1.7%, and 2.8% of DRG neurons innervating the femur, in control, sham-operated, and OVX rats, respectively. The proportion of TRPV1-ir neurons in DRG innervating the femur in OVX rats was significantly higher than that in control and sham-operated rats (p<0.05). CONCLUSION: Under physiological conditions, DRG neurons innervating femurs in rats contain TRPV1. Osteoporosis increases the numbers of TRPV1-ir neurons in DRG innervating osteoporotic femurs in rats. These findings suggest that TRPV1 may have a role in sensory perception of osteoporotic femurs.

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.

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.

PURPOSE: Patients with idiopathic carpal tunnel syndrome are commonly treated by steroid injections into the carpal tunnel. We administered triamcinolone (Tr) to chronic constriction injury model rats. We hypothesized that Tr administration would have both favorable behavioral effects and quantifiable immunohistological effects on compressed nerves. METHODS: Thirty-six male Wister rats were used. For rats to be treated with Tr, we loosely ligated their right sciatic nerves at 4 sites. Sham rats had their nerves exposed without ligation. On postoperative day 7, we reexposed their ligated nerves, after which we delivered either 0.1 mg of Tr (0.1-mg group), 0.5 mg of Tr (0.5-mg group), or normal saline (saline group) around the nerve fibers at the injured sites. Gait was analyzed, and allodynia was assessed with von Frey hairs, before surgery and on postoperative days 3, 7, 10, 14, and 21. The right sciatic nerve was resected and stained using hematoxylin-eosin, and the fourth and fifth lumbar dorsal root ganglia (DRG) were removed and assessed by immunohistochemistry for calcitonin gene-related peptide (CGRP) and activating transcription factor 3 (ATF3) on postoperative day 21. In addition, interleukin-1β (IL-1β) in sciatic nerve was quantified using enzyme-linked immunosorbent assays. RESULTS: Mechanical allodynia was significantly decreased in the 0.5-mg group compared with the saline group. In hematoxylin-eosin sections, the extent of inflammation-induced edema between the nerve fibers and infiltration of inflammatory cells was significantly reduced in the 0.5-mg group compared with the saline group. IL-1β levels at the sciatic nerve in the 0.5-mg group were significantly lower than those in the saline group. CONCLUSIONS: Tr-treated chronic constriction injury rats exhibited significant alleviation of sensory disturbance, edema, inflammation, and pain-related peptide upregulation. These phenomena suggest the validity of Tr administration as a treatment affecting the nerve itself. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

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.

STUDY DESIGN: Immunohistological analysis of the cervical dorsal root ganglia (DRG). OBJECTIVE: To investigate immunohistologically in rats whether intradiscal administration of anti-nerve growth factor (NGF) antibody in injured cervical intervertebral discs (IVDs) suppresses pain-related peptide expression in DRG neurons. SUMMARY OF BACKGROUND DATA: Neck pain can involve the entire neck and become chronic and intractable. Cervical disc degeneration is a primary cause of neck pain, and pain-related mediators, such as NGF, have been correlated with discogenic pain. METHODS: We examined Sprague-Dawley rats that received 10 punctures in the C5-C6 IVD, and were treated with saline (puncture group) or an anti-NGF antibody (anti-NGF group). The retrograde neurotracer Fluoro-Gold (FG) was then injected into the C5-C6 IVD. In addition, we examined a sham group that did not receive punctures (disc nonpuncture). The C2-C7 DRG were harvested 1 week after surgery and immunostained for calcitonin gene-related peptide (CGRP), a marker for peptide-containing neurons. We determined for each group the percentages of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-ir). RESULTS: FG-labeled neurons innervating the C5-C6 IVD were found in all C2-C7 DRG examined. The percentage of FG-labeled CGRP-ir DRG neurons in the puncture group was significantly higher than that observed in the sham (P < 0.001) and anti-NGF groups (P < 0.001), but there was no significant difference between the sham and anti-NGF groups (P > 0.05). Therefore, intradiscal administration of anti-NGF antibody suppressed CGRP expression the cervical DRG. CONCLUSION: Neurons located in the C2-C7 DRG innervated the C5-C6 IVD. These findings indicate that neck pain may be derived from degenerated IVDs. Furthermore, intradiscal administration of anti-NGF antibody suppressed CGRP expression in the cervical DRG innervating the injured IVD. Therefore, inhibiting NGF upregulation in the cervical IVD may be an efficient treatment for discogenic neck pain. LEVEL OF EVIDENCE: N/A.

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.

PURPOSE: To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS. MATERIALS AND METHODS: The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment. RESULTS: The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122). CONCLUSION: The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.