中村 順一

BACKGROUND: The prognosis of Legg-Calvé-Perthes disease (LCPD) in young patients has been accepted as favorable. The purpose of this study was to clarify the outcome of LCPD patients with onset before 6 years of age. METHODS: From 1989 to 2007, of 332 LCPD patients, 114 hips (in 100 patients) were diagnosed before 6 years of age (mean age, 4.5 y old) with subsequent repair of the epiphysis in all cases. Waldenström classification at presentation was initial stage in 76 hips and fragmentation stage in 38 hips. Lateral pillar classification was group A in 17 hips, group B in 22 hips, group B/C in 24 hips, and group C in 51 hips. Treatment methods were observation with restriction of activity alone in 42 hips and several containment treatments in 72 hips. RESULTS: At the mean age of 14, Stulberg classification was class I in 26 hips, II in 46 hips, III in 28 hips, and IV in 14 hips. These data show an acceptable outcome in 72 of 114 hips (63%). Logistic regression analysis revealed that lateral pillar classification (odds ratio, 3.6) and good range of abduction without treatment (odds ratio, 4.0) were prognostic factors. CONCLUSIONS: Poor outcome was observed even in patients before 6 years of age with large necrotic area. Lateral pillar classification and good range of abduction were prognostic factors. LEVEL OF EVIDENCE: Level IV. Therapeutic studies-investigating the results of treatment. Case series.

Background: Nontraumatic osteonecrosis of the femoral head (ONFH) is a rare disorder caused by ischemic necrosis of unknown etiology. A few studies have demonstrated trends in the number of patients with ONFH. However, there are no data on temporal trends in characteristics such as age, gender, and causative factors. To investigate this, we examined data from a multicenter hospital-based sentinel monitoring system in Japan. Methods: A total of 3041 newly-diagnosed ONFH patients from 34 participating hospitals who were reported to the system from 1997-2011 were analyzed. We examined age at diagnosis, potential causative factors, and underlying diseases for which patients received systemic steroid administration. Their temporal trends were assessed according to date of diagnosis in 5-year intervals (1997-2001, 2002-2006, and 2007-2011). Results: The gender ratio and distribution of potential causative factors did not change. Regarding underlying diseases requiring steroid administration, the proportion of patients with systemic lupus erythematosus decreased in males (10% to 6.4%) and in females (37% to 29%). Proportion of patients with renal transplantation fell consistently across the study period in both males (3.8% to 1.2%) and females (3.2% to 0.8%). In contrast, the proportion of patients receiving steroids for pulmonary disease (except asthma) significantly increased in both males (0.5% to 5.5%) and females (0.5% to 3.6%). Conclusions: This large descriptive study is the first to investigate temporal trends in the characteristics of ONFH, which provide useful information for future studies.

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.

OBJECTIVES: To document the reliability of Abe's classification and to clarify the predictive factors for acetabular labral lesions in osteoarthritis of the hip with radial magnetic resonance (MR) imaging. METHODS: Reliability trial for the classification of acetabular labral lesion was performed by six orthopedic surgeons, grading 20 radial MR images in a blinded fashion at an interval of 4-5 weeks. Radial MR images of 275 hips in 263 patients were prospectively analyzed to determine the relationship between acetabular labral lesions, their distribution, age, and the acetabular coverage. RESULTS: Cohen's quadratic weighted kappa of inter-observer reliability was 0.784 for the grade and 0.812 for the shape category. The weighted kappa of intra-observer reliability was 0.852 for the grade and 0.90 for the shape category. Multiple regression analysis revealed that both the grade and the shape were associated with age, acetabular coverage, and location of the labrum. CONCLUSIONS: Abe's classification of labral lesions was reliable for both the grade and shape categories. Aging, acetabular dysplasia, and the anterosuperior portion would be predictive factors for degeneration of the acetabular labrum using radial MR imaging.

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.

BACKGROUND: In situ fixation (ISF) is standard treatment for slipped capital femoral epiphysis (SCFE) to stabilize the epiphysis and to prevent further slip. The aim of this study was to clarify the incidence of slip progression after ISF and its prognostic factors. METHODS: We retrospectively reviewed 53 hips in 49 consecutive SCFE patients who underwent single screw ISF and were followed until physeal closure. Clinical and radiographic findings were viewed to assess progression of the posterior tilting angle (PTA). RESULTS: Mean PTA was 33.4 degrees (range, 18 to 75 degrees) at ISF and 35.9 degrees (range, 18 to 75 degrees) at physeal closure with progression of PTA of 2.5 degrees (range, -2 to 19 degrees). Slip progression occurred in 28 of 53 hips (53%), and more than five degrees of progression occurred in 14 hips (26%). Multiple regression analysis revealed that point of screw insertion (one point for lateral and two points for medial) was a significant prognostic factor for progression of the slip by the following formula: (progression of PTA) = -1.523 + 2.701 × (point of screw insertion), R(2) = 0.148, p = 0.005. CONCLUSIONS: The current study showed that a screw inserted from the lateral side to the intertrochanteric line prevented postoperative slip progression.

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.

STUDY DESIGN: Animal study. OBJECTIVE: To investigate pain-related expression of NaV1.7 in dorsal root ganglia (DRG) innervating intervertebral discs. SUMMARY OF BACKGROUND DATA: The pathophysiology of discogenic low back pain is not fully understood. Prostaglandins and cytokines produced by degenerated discs can cause pain, but nonsteroidal anti-inflammatory and steroid medications are often ineffective at pain reduction. Tetrodotoxin-sensitive, voltage-gated sodium (NaV) channels are associated with sensory transmission in primary sensory nerves, and the NaV1.7 channel has emerged as an attractive analgesic target. The purpose of this study was to investigate pain-related expression of NaV1.7 in DRG innervating intervertebral discs. METHODS: Using a rodent model of disc puncture, we labeled DRG neurons innervating L5-L6 discs with FluoroGold neurotracer (n = 20). Half of the rats (n = 10) underwent intervertebral disc puncture using a 23-gauge needle (puncture group), and the other half underwent non-puncture sham surgery (non-puncture group). Seven and 14 days after surgery, DRGs from the L1 to L6 levels were harvested, sectioned, and immunostained for NaV1.7, and the proportion of NaV1.7-immunoreactive DRG neurons was evaluated. RESULTS: NaV1.7 was expressed in DRG neurons innervating intervertebral discs from L1 to L5. The ratio of NaV1.7-expressing DRG neurons to total FG-labeled neurons was 7.2% and 7.6% at 1 and 2 weeks after surgery, respectively, in the non-puncture group and 16.2% and 16.3% at 1 and 2 weeks, respectively, in the puncture group. The upregulation of NaV1.7 after puncture was significant at both 1 and 2 weeks after surgery (P < 0.01). CONCLUSION: We found that disc injury increases NaV1.7 expression in DRG neurons innervating injured discs. NaV1.7 may be a therapeutic target for pain control in patients with lumbar disc degeneration.

STUDY DESIGN: Animal study. OBJECTIVE: To evaluate pain behavior and neuropeptide changes in the spinal dorsal horn after sciatic nerve compression and application of nucleus pulposus (NP) in rats. SUMMARY OF BACKGROUND DATA: The pathomechanisms of lumbar disc herniation pain have not been fully elucidated. Pain-associated neuropeptides, including substance P and calcitonin gene-related peptide (CGRP), are produced in dorsal root ganglion neurons and transported to spinal dorsal horn nerve terminals where they function in pain transmission. However, changes in CGRP-immunoreactive (IR) sensory nerve terminals have not been reported in models of disc herniation. This study evaluated pain-related behavior and changes in CGRP-IR terminals in the spinal dorsal horn after combined sciatic nerve compression and NP application. METHODS: Five groups of rats underwent either sciatic nerve compression with NP (n = 20), application of NP only (n = 20), nerve compression only (n = 20), and sham operation with neither compression nor NP (n = 20) or no operation (controls, n = 20). Mechanical hyperalgesia was measured every second day for 3 weeks. CGRP-IR terminals in each spinal dorsal horn lamina were examined 7 and 14 days postsurgery. Pain behavior and CGRP immunoreactivity were compared among the 5 groups. RESULTS: Mechanical hyperalgesia was found in the NP only, nerve compression only, and the NP with nerve compression groups (P ≤ 0.05). CGRP-IR nerve terminals in the superficial laminae (I and II) and the deep laminae (III-VI) significantly increased in the NP only, nerve compression only, and NP with nerve compression groups compared with control and sham groups (P ≤ 0.05). Significant mechanical hyperalgesia and increased CGRP-IR nerve terminals were found in the NP with nerve compression group compared with the NP only and nerve compression only groups (P ≤ 0.05). CONCLUSION: Our results indicate that nerve compression plus NP application produces the most pain-related behavior. CGRP-IR nerve terminals increased in laminae I and II that transmit pain and in laminae III to VI that transmit proprioception. Findings suggest that nerve compression plus NP application induces changes in CGRP expression in the superficial and deep laminae, and these changes are partly responsible for disc herniation pain.

OBJECTIVE: Hypervascularization in finger clubbing is recognized, but its microanatomical basis remains unclear. This pilot descriptive study used magnetic resonance imaging (MRI) to explore this further. METHODS: High-resolution MRI acquired with contrast agent was carried out in 4 patients with finger clubbing and 4 healthy volunteers. The anatomy of the nail bed, capsular structures, and bony changes were described. RESULTS: Marked nail bed thickening and contrast enhancement was noted in all clubbed fingers, with bone edema in 3 of the 4 patients. None of the healthy subjects had similar abnormalities. CONCLUSION: This confirms that hypervascularization of the nail bed observed in the microanatomy on high-resolution MRI is associated with clubbed appearances of the nails.

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.

PURPOSE: The pathomechanisms of pain resulting from lumbar disc herniation have not been fully elucidated. Prostaglandins and cytokines generated at the inflammatory site produce associated pain; however, non-steroidal anti-inflammatory drugs and steroids are sometimes ineffective in patients. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are related to sensory transmission in primary sensory nerves. The sodium channel NaV1.7 has emerged as an attractive analgesic target. The purpose of this study was to evaluate pain-related behavior and expression of NaV1.7 in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. METHODS: Rats were divided into three groups and underwent either sciatic nerve compression with NP for 2 s using forceps (n = 20), sham operation with neither compression nor NP (n = 20), or no operation (controls, n = 20). Mechanical hyperalgesia was measured every second day for three weeks using von Frey filaments. NaV1.7 expression in L5 DRG was examined 7 and 14 days after surgery using immunohistochemistry. The number of neurons immunoreactive for NaV1.7 was compared among the three groups. RESULTS: Mechanical hyperalgesia was found over the 14-day observation in the nerve compression plus NP application group, but not in the sham-operated or control groups (P < 0.05). NaV1.7 expression in L5 DRG was up-regulated in the nerve compression plus NP application group, compared with sham-operated and control rats (P < 0.01). CONCLUSIONS: Our results indicate that nerve compression plus NP application produces pain-related behavior. We conclude that NaV1.7 expression in DRG neurons may play an important role in mediating pain from sciatic nerves after compression injury and exposure to NP.

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.

Extreme lateral interbody fusion (XLIF) has been widely used for minimally invasive anterior lumbar interbody fusion (ALIF), but an approach to L5-S1 is difficult because of the iliac crest. In the current study, we present 2 cases using minimally invasive oblique lateral interbody fusion (OLIF) of L5-S1. The patients showed foraminal stenosis between L5 and S1 and severe low back and leg pain. The patients were placed in a lateral decubitus position and underwent OLIF surgery (using a cage and bone graft from the iliac crest) without posterior decompression. Posterior screws were used in the patients. Pain scores significantly improved after surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. OLIF surgery was minimally invasive and produced good surgical results without complications.

STUDY DESIGN: Animal study. OBJECTIVE: To determine the existence of dichotomizing sensory nerve fibers innervating both the lumbar vertebral body and the area surrounding the iliac crest (ASIC). SUMMARY OF BACKGROUND DATA: Elderly patients with osteoporosis sometimes experience lumbar vertebral fracture and may feel diffuse nonlocalized pain in the back, the lateral portion of the trunk, and the ASIC. The pattern of sensory innervation of vertebral bodies remains unclear. DRG neurons with dichotomizing axons have been reported and are thought to be related to referred pain. The purpose of this study was to investigate the existence of dichotomizing axons to the lumbar vertebral bodies and the ASIC in rats. METHODS: Two kinds of neurotracers (1,1´-dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate [DiI] and Fluoro-Gold [FG]) were used. DiI crystals were placed in the left ASIC, and FG was applied into the L2 vertebral body in 10 rats. Four weeks later, left DRGs from L1 to L6 were resected, sectioned, and observed under a fluorescence microscope. RESULTS: DiI-labeled DRG neurons innervating the ASIC and FG-labeled DRG neurons innervating the vertebral L2 body were distributed from L1 to L6. The ratio of total double-labeled per total DiI-labeled DRG neurons was 10.2%, and that of total double-labeled per total FG-labeled DRG neurons was 14.7%. These double-labeled DRG neurons innervating the L2 vertebral body had other axons that extended to the ASIC. CONCLUSION: This finding provides a possible neuroanatomical explanation for referred pain in the ASIC from vertebral bodies.

BACKGROUND: Previous studies reported that the publication rate of abstracts presented at overseas meetings was around 50 %. The study objectives were to determine the rate of publication in English-language journals and the impact factor (IF) for all papers presented at the Annual Meeting of the Japanese Orthopaedic Association (JOA) and Annual Research Meeting of the Japanese Orthopaedic Association (JOAR), and to compare the publication rates and IFs from abstracts accepted for oral versus poster presentations. METHODS: Titles and first authors were identified for 1,676 abstracts of free papers accepted for presentation to the JOA in 2006 and 2007, and 1,529 abstracts to the JOAR from 2006 to 2008. We identified the associated journal publications by searching PubMed, and IFs were determined using the journal citation reports. The publication rates and IFs for papers accepted for oral versus poster presentations were compared using statistical analysis. RESULTS: The overall publication rate was 25.5 % from the JOA and 50 % from the JOAR. There were no significant differences in yearly publication rates, or between oral and poster presentations for each year. The average IFs for all publications from the JOA was 2.45 and that from the JOAR was 3.5. There were no significant differences in yearly IFs, or between oral and poster presentations for each year (P > 0.05). CONCLUSIONS: The rate from JOAR was similar to publication rates for abstracts presented at overseas orthopedic meetings, however, the rate from JOA was half that of publication rates for abstracts presented at overseas orthopedic meetings, indicating that JOA may provide a below average contribution of new medical data to the international scientific community. No significant difference in publication rates between oral and poster presentations were found, and this suggests a need for improvement of the review system for the annual meeting and that review scores at the meetings did not predict the publication fate of abstracts.

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.

STUDY DESIGN: Prospective study of changes in intervertebral disc degeneration after injection of bupivacaine. PURPOSE: To examine whether injection of bupivacaine into human intervertebral discs accelerates their degeneration. OVERVIEW OF LITERATURE: Bupivacaine is commonly used for therapy and diagnosis of discogenic low back pain. However, several in vitro studies have reported toxic effects of bupivacaine to disc cells. We sought to evaluate whether this finding is clinically relevant. METHODS: We selected 46 patients with low back pain who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging (MRI) (discography group, n=18), discoblock group (injection of bupivacaine, n=18), and a control group, n=10). There were no significant differences in baseline characteristics across the 3 groups. The two experimental groups underwent either discography or anesthetic discoblock, respectively. All three groups were followed up 5 years after the examination. RESULTS: At 5 years follow-up, there was no significant difference in the rate of disc degeneration among the 3 groups (p>0.1). Moreover, X-ray images showed that there was no significant difference in disc height, range of motion, or translation between flex and extension position (p>0.1). CONCLUSIONS: In conclusion, radiologic and MRI findings did not show acceleration of intervertebral disc degeneration at 5 years after a single injection of bupivacaine into human discs.

STUDY DESIGN: Prospective study. OBJECTIVE: To examine the efficacy of teriparatide or bisphosphonate treatment to reduce pedicle screw (PS) loosening after instrumented lumbar posterolateral fusion in postmenopausal women with osteoporosis. SUMMARY OF BACKGROUND DATA: Failure of fixation caused by loosening of PSs in osteoporosis is a problem in spinal surgery. Oral administration of bisphosphonate or intermittent injection of parathyroid hormone treatment increases bone mass and reduces the risk of osteoporotic vertebral fractures. Although these treatments may be factor in improving bone quality, a clinical study of the efficacy of bisphosphonate or parathyroid hormone for reducing PS loosening that addresses the quality of the bone marrow and pedicle cortex has not yet been reported. METHODS: Sixty-two women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 3 groups: a teriparatide group (daily subcutaneous injection of 20 μg of teriparatide, n = 20), a bisphosphonate group (daily oral administration 2.5 mg of risedronate, n = 20), and a control group (without medication for osteoporosis, n = 22). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Loosening of PSs and surgical outcome were evaluated radiographically, clinically, and by computed tomography 12 months after surgery. RESULTS: At 12-month follow-up, the incidence of PS loosening was 7% to 13% in the teriparatide group, 13% to 26% in the risedronate group, and 15% to 25% in the control group. The incidence of PS loosening in the teriparatide group was significantly lower than that in the risedronate or the control group (P < 0.05). In contrast, the extent of PS loosening in the risedronate group was not significantly different from that in the control group (P > 0.05). CONCLUSION: Our findings suggest that administration of teriparatide increased the quality of the lumbar spine bone marrow and pedicle cortex.

STUDY DESIGN: Immunohistochemistry for tumor necrosis factor (TNF)-α in nucleus pulposus of adolescent patients with lumbar disc herniation. OBJECTIVE: To examine whether an inflammatory cytokine is expressed in the nucleus pulposus of adolescent patients with lumbar disc herniation. SUMMARY OF BACKGROUND DATA: TNFα is thought to play a crucial role in the radicular pain caused by lumbar disc herniation in adult patients. However, the expression of TNFα in the nucleus pulposus of adolescent patients with lumbar disc herniation has not been explored. METHODS: Five samples of nucleus pulposus from adolescent patients with lumbar disc herniation (age, 12-16 yr; n = 5) or controls requiring surgery for other back problems (age, 12-16 yr; n = 4; nonpainful scoliosis) were harvested during surgery. Nucleus pulposus specimens were immunostained using TNFα antibodies and immunostained cells in the nucleus pulposus were counted. We compared the expression of TNFα between the 2 groups. RESULTS: In patients with lumbar disc herniation, more TNFα-immunoreactive cells were seen in the nucleus pulposus in comparison with patients with nonpainful scoliosis (P < 0.01). CONCLUSION: The results suggest that TNFα may play a role in adolescent patients with lumbar disc herniation. The TNFα expression may be related with disc degeneration and pain in adolescent patients with lumbar disc herniation.

INTRODUCTION: There have been few reports of patients with bilateral cervical facet dislocations that remain untreated for eight weeks or more. We report the case of a 76-year-old man with an old bilateral cervical facet joint dislocation fracture that was treated by posterior-anterior reduction and fixation. CASE PRESENTATION: A 76-year-old Asian man was involved in a road traffic accident. He presented with neck pain and arm pain on his right side, but motor weakness and paralysis were not observed. He was treated conservatively; however, instability and spondylolisthesis at the C5 to C6 joint increased eight weeks after the injury. We performed a posterior-anterior reduction and fixation. After surgery, bony union was achieved, and his neck pain and arm pain disappeared. CONCLUSION: We recommend reduction and fixation surgery if a patient has an old bilateral facet joint dislocation fracture in the cervical spine.

OBJECTIVES: Our aim was to clarify the distribution of hip pain in patients with osteoarthritis of the hip secondary to developmental dysplasia of the hip (DDH). METHODS: We retrospectively studied 443 hips in 369 patients with osteoarthritis secondary to DDH; mean age was 61 years, and follow-up rate was 84 %. Hip pain was defined as preoperative pain that was relieved 3 months after total hip arthroplasty. RESULTS: Distribution of pain originating in the hip was 89 % (393 hips) to the groin, 38 % (170 hips) to the buttock, 33 % (144 hips) to the anterior thigh, 29 % (130 hips) to the knee, 27 % (118 hips) to the greater trochanter, 17 % (76 hips) to the low back, and 8 % (34 hips) to the lower leg. When the groin, buttock, and greater trochanter were combined as the hip region, 95 % (421 hips) of pain was located in the hip region. On the other hand, when the anterior thigh, knee, lower leg, and low back were combined as the referral region, 55 % (242 hips) showed referred pain. CONCLUSIONS: We suggest that rheumatologists be aware of hip disease masquerading as knee pain or low back pain.

Adult presentation of neglected congenital muscular torticollis (CMT) is rare. Therefore, efficacy of surgical treatment for adult CMT is unclear. We experienced a case of neglected CMT in a 28-year-old male patient and report the surgical result here. We conducted unipolar resection at the distal end of the sternocleidomastoid muscle (SCM). After surgery, the range of neck movement and head tilt improved, and his appearance was cosmetically improved despite the long-standing nature of the deformity. We concluded that surgical management of adult patients with neglected congenital muscular torticollis may be a treatment option.

A 26-year-old paraplegic schizophrenic Japanese woman suffered from severe kyphosis and back pain derived from lumbar burst fractures caused by jumping. She had already undergone resection of the L1 and L2 spinous processes for sharp angular kyphosis, but she still had severe kyphosis and back pain at the L1 and L2. Radiographical examination revealed fused anterior columns at L1 and L2 with severe local kyphosis and a significantly decreased percutaneous distance in the back. The patient underwent anterior instrumented bony resection including an L2 vertebral osteotomy: bilateral L2-L3 facetectomy and partial posterior osteotomy of the L2 vertebrae via a posterior approach followed by an anterior corpectomy of the L2 vertebrae and insertion of a cylindrical cage. No posterior instrumentation was used owing to the presence of atrophied paraspinal soft tissues. Lumbar interbody fusion was performed with vertebral body screws extending from T12 to L4 and corresponding anterior distension and posterior compression. The procedure corrected the kyphosis by 15° and enhanced local stability. Postsurgical visual analogue scale improved from 9.0 to 2.0 and Oswestry Disability Index from 40 to 17.8, respectively. In conclusion, we have demonstrated that anterolateral interbody fusion using extended fixation can compensate for posterior corrective surgery.

Introduction. Spinal scoliosis and kyphosis in elderly people sometimes cause severe low back pain. Surgical methods such as osteotomy are useful for correcting the deformity. However, complications during and after surgery are associated with the osteotomy procedure. In particular, it is difficult to manage deformity correction surgery for patients with Parkinson's disease. Here, we present two cases of combined anterior and posterior surgery for deformity in patients with adult scoliosis and kyphosis due to Parkinson's disease. Case Presentation. Two 70-year-old women had spinal scoliosis and kyphosis due to Parkinson's disease. They had severe low back pain, and conservative treatment was not effective for the pain. Surgery was planned to correct the deformity in both patients. We performed combined posterior and anterior correction surgery. At first, posterior fusions were performed from T4 to the ilium using pedicle screws. Next, cages and autograft from the iliac crest were used in anterior lumbar surgery. The patients became symptom free after surgery. Bony fusion was observed 12 months after surgery. Conclusions. Combined posterior and anterior fusion surgery is effective for patients who show scoliosis and kyphosis deformity, and symptomatic low back pain due to Parkinson's disease.

STUDY DESIGN: Case series. OBJECTIVE: To present the difficulty of diagnosing the origin of lower leg pain in patients with lumbar spinal stenosis and hip joint arthritis. SUMMARY OF BACKGROUND DATA: Pain arising from a degenerated hip joint is sometimes localized to the lower leg. Patients with lumbar spinal disease may also show radicular pain corresponding to the lower leg area. If patients present with both conditions and only pain at the lower leg, it is difficult to determine the origin of the pain. METHODS: We reviewed 420 patients who had leg pain with lumbar spinal stenosis diagnosed by myelography, computed tomography after myelography, or magnetic resonance imaging. Pain only at the ipsilateral lateral aspect of the lower leg but slight low back pain or pain around the hip joint was shown in 4 patients who had lumbar spinal stenosis and hip osteoarthritis. The symptoms resolved after L5 spinal nerve block, but remained after lidocaine infiltration into the hip joint. We performed decompression and posterolateral fusion surgery for these 4 patients. RESULTS: Leg pain did not resolve after lumbar surgery in all patients. Conservative treatment was not effective from 6 to 12 months, so ultimately we performed ipsilateral total hip replacement for all patients and they became symptom-free. CONCLUSION: It is difficult to determine the origin of lower leg pain by spinal nerve block and hip joint block in patients with lumbar spinal stenosis and hip osteoarthritis. We take this into consideration before surgery.

STUDY DESIGN: A case report. OBJECTIVE: An elderly patient presented with an acute lumbar spinal pseudogout attack after lumbar instrumented surgery. SUMMARY OF BACKGROUND DATA: Although gout and pseudogout are common diseases causing inflammatory arthropathy in peripheral joints, involvement of the spine is uncommon. Here, we report a patient experiencing an acute lumbar spinal pseudogout attack after lumbar instrumented surgery. METHODS: The patient was treated for lumbar spondylolisthesis at L4 and L5 level and afterward complained of lower back and bilateral leg pain. Conservative treatment was not effective for the patient; therefore, we preformed posterior transforaminal lumbar interbody fusion surgery. RESULTS: The postoperative course was uneventful; however, he experienced lower back pain 4 weeks after surgery. Magnetic resonance image showed changes in signal intensities of vertebra and fluid accumulation in posterior back muscles. A biopsy was performed, but the culture was negative for infection. Calcium pyrophosphate dehydrate was detected in the fluid. Thus, conservative therapy without antibiotics was performed, and the patient's symptoms disappeared within 2 weeks. CONCLUSION: Here, we reported the first case of acute lumbar spinal pseudogout attack after lumbar instrumented surgery. We recommend considering pseudogout before and after surgery.

UNLABELLED: In the present case of postoperative lumbar spinal stenosis after non-instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone union was not completed and the patient felt the recurrence of his symptoms within two years. We performed re-decompression with fusion, and in hematoxylin and eosin staining of HA granulation harvested during revision surgery, fibrous tissue with hyaline degeneration surrounded the cavity where the HA had existed. Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal layer of the cavity, and no obvious bony bridge had regenerated from autologous bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be seen in the new bone, suggesting that the activity of osteoclasts in the new bone decreased during the seven years after the primary surgery. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3483360258050263.

STUDY DESIGN: Prospective trial. OBJECTIVE: To examine the clinical efficacy of teriparatide for bone union after instrumented lumbar posterolateral fusion using local bone grafting in women with postmenopausal osteoporosis. SUMMARY OF BACKGROUND DATA: Intermittent parathyroid hormone (PTH) treatment increases bone mass and reduces the risk for osteoporotic vertebral fractures. Recombinant human PTH (1-34) has already been approved as a treatment for severe osteoporosis. Preclinical data support the efficacy of PTH for lumbar spinal fusion. However, clinical results of PTH for spinal fusion have not yet been reported. METHODS: Fifty-seven women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 2 treatment groups, a teriparatide group (n = 29; daily subcutaneous injection of 20 μg of teriparatide) and a bisphosphonate group (n = 28; weekly oral administration of 17.5 mg of risedronate). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Fusion rate, duration of bone union, and pain scores were evaluated 1 year after surgery. RESULTS: Pain scores improved after surgery; however, no significant difference was noted between the groups after surgery. The rate of bone union was 82% in the teriparatide group and 68% in the bisphosphonate group. Average duration of bone union was 8 months in the teriparatide group and 10 months in the bisphosphonate group. The rate of bone union and average of duration of bone union in the teriparatide group patients were significantly superior to those in the bisphosphonate group. CONCLUSION: Daily subcutaneous injection of teriparatide for bone union using local bone grafting after instrumented lumbar posterolateral fusion in women with postmenopausal osteoporosis was more effective than oral administration of bisphosphonate.

INTRODUCTION: Interleukin-6 (IL-6) is thought to play a crucial role in the radicular pain caused by lumbar spinal stenosis. However, efficacy of inhibition of IL-6 for sciatica in patients with lumbar spinal stenosis has not been clarified. The purpose of the current study was to examine the effect of the anti-IL-6 receptor monoclonal antibody, tocilizumab, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. METHODS: Sixty patients with low back and radicular leg pain caused by spinal stenosis were investigated. In 30 patients, we infiltrated 2.0 mL of lidocaine and 80 mg of tocilizumab onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone were used in 30 patients. Low back pain, leg pain, and leg numbness were evaluated during 1 month after spinal nerve infiltration. RESULTS: Infiltration of tocilizumab was more effective than dexamethasone for leg pain (3 days, 1, 2, and 4 weeks), low back pain (3 days, 1, 2 and 4 weeks), and leg numbness (3 days, 1 and 2 weeks). No adverse event was observed in either group. CONCLUSION: Our results indicate that the epidural administration of an anti-IL-6 receptor monoclonal antibody, tocilizumab, onto the spinal nerve produced reduction of radicular leg pain, numbness, and low back pain without adverse event. IL-6 may be one of the inducers of pain caused by spinal stenosis in humans.

It is known that free nerve endings are degenerated after application of shock waves. We therefore hypothesized that the application of shock waves to muscle induces dysfunction of neuromuscular transmission at neuromuscular junctions. We investigated changes in neuromuscular transmission in response to shock wave application. Sprague-Dawley rats were used in this study. Two thousand shock waves at an energy flux density of 0.18 mJ/mm(2) were applied to their right calf muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using rhodamine-α-bungarotoxin on the day of treatment (n  =  5). Amplitude and latency of compound muscle action potentials were measured on the day of treatment and 1, 2, 4, 6, and 8 weeks after treatment (n  =  10, each group). Degenerated acetylcholine receptors existed in all treated muscles. Although the action potential amplitude on the treated side was significantly less than on the control side from the day of treatment (25.1 ± 7.8 vs. 34.5 ± 9.1, p  =  0.012) to 6 weeks (27.9 ± 7.2 vs. 34.5 ± 7.2, p  =  0.037), there was no significant difference at 8 weeks. There was no significant difference in transmission latency between the groups. The application of shock waves to muscle induced a transient dysfunction of nerve conduction at neuromuscular junctions.

OBJECTIVE: To clarify the sensory innervation and inflammatory cytokines in hypertrophic synovia associated with pain transmission in OA of the hip. METHODS: A piece of the synovium was extracted during reconstruction surgery in 50 patients with OA of the hip as an inflammatory synovium and in 12 patients with femoral neck fracture as a normal synovium. Each sample was immersed in fixative solution, sectioned on a cryostat, and then processed for immunohistochemistry using antibodies as follows: neuron-specific class III β-tubulin (TuJ-1) as a general marker for nerve fibres, calcitonin gene-related peptide (CGRP) for sensory nerve fibres, nuclear factor κB (NF-κB) for the protein complex controlling the transcription of DNA in cellular responses to painful stimuli, and TNF-α for cytokines involved in acute inflammation. The number of immunopositive cells and fibres were counted using a fluorescence microscope. RESULTS: In the inflammatory synovium of OA of the hip, TuJ-1 was positive in 46% (23 hips). Of those positive for TuJ-1, 78% (18 hips) were also positive for CGRP, but 22% (5 hips) were negative for CGRP. NF-κB was positive in 68% (34 hips). Of those positive for NF-κB, 76% (26 hips) were also positive for TNF-α, but 24% (8 hips) were negative for TNF-α. In normal synovia, all four substances were negative. CONCLUSION: We suggest sensory innervation and inflammatory cytokines in hypertrophic synovia are associated with nociception in OA of the hip. TRIAL REGISTRATION: University Hospital Medical Information Network, www.umin.ac.jp, UMIN000001335.

STUDY DESIGN: An immunohistological analysis of the cervical intervertebral disc (IVD). OBJECTIVE: To investigate sensory and autonomic innervation of the rat cervical IVD. SUMMARY OF BACKGROUND DATA: Many clinicians are challenged with treating wide-ranging chronic neck pain. Several authors have reported that sympathetic nerves participate in chronic pain, and various sympathectomy procedures can effectively treat chronic pain. METHODS: The neuro-tracer Fluoro-gold (FG) was applied to the anterior surfaces of C5-C6 IVDs from 10 Sprague-Dawley rats to label the neurons of the innervating dorsal root ganglion (DRG), stellate ganglion (SG; sympathetic ganglion), and nodose ganglion (NG; parasympathetic ganglion). Seven days postsurgery, DRGs from level C1-C8, SG, and NG neurons were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP; a marker for peptide-containing neurons) and isolectin B4 (IB4; a marker for nonpeptide-containing neurons). The proportion of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-IR), IB4-binding, and non-CGRP-IR and IB4-binding, and the proportion of FG-labeled SG neurons and NG neurons were calculated. RESULTS: FG-labeled neurons innervating the C5-C6 IVD were distributed throughout the C2-C8 DRGs. The proportions of FG-labeled DRG neurons that were CGRP-IR, IB4-binding, non-CGRP-IR and IB4-binding, as well as SG neurons, and NG neurons were 20.6%, 3.3%, 55.7%, 8.9%, and 11.5%, respectively. The proportion of CGRP-IR FG-labeled DRG neurons was significantly higher than the proportion of IB4-binding FG-labeled DRG neurons at each level (P < 0.05). CONCLUSION: The C5-C6 IVD was innervated multisegmentally from neurons of the C2-C8 DRG, SG, and NG. Overall, 79.6% of the nerve fibers innervating the IVD were sensory nerves and 20.4% were autonomic nerves. Furthermore, 23.9% of the nerve fibers innervating the IVD were afferent sensory pain-related nerves, 8.9% were efferent sympathetic nerves, and 11.5% were efferent parasympathetic nerves. These findings may explain the wide-ranging and chronic discogenic pain that occurs via the somatosensory and autonomic nervous system.

PURPOSE: Chronic low back pain is a common clinical problem. As medication, non-steroidal anti-inflammatory drugs are generally used; however, they are sometimes non-effective. Recently, opioids have been used for the treatment of chronic low back pain, and since 2010, transdermal fentanyl has been used to treat chronic non-cancer pain in Japan. The purpose of the current study was to examine the efficacy of transdermal fentanyl in the treatment of chronic low back pain. MATERIALS AND METHODS: This study included patients (n=62) that suffered from chronic low back pain and were non-responsive to non-steroidal anti-inflammatory drugs. Their conditions consisted of non-specific low back pain, multiple back operations, and specific low back pain awaiting surgery. Patients were given transdermal fentanyl for chronic low back pain. Scores of the visual analogue scale and the Oswestry Disability Index, as well as adverse events were evaluated before and after therapy. RESULTS: Overall, visual analogue scale scores and Oswestry Disability Index scores improved significantly after treatment. Transdermal fentanyl (12.5 to 50 μg/h) was effective in reducing low back pain in 45 of 62 patients; however, it was not effective in 17 patients. Patients who experienced the most improvement were those with specific low back pain awaiting surgery. Adverse events were seen in 40% of patients (constipation, 29%; nausea, 24%; itching, 24%). CONCLUSION: Transdermal fentanyl significantly improved visual analog scale scores and Oswestry Disability Index scores in 73% of patients, especially those with specific low back pain awaiting surgery; however, it did not decrease pain in 27% of patients, including patients with non-specific low back pain or multiple back operations.

PURPOSE: Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. MATERIALS AND METHODS: Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman's correlation coefficient by rank test. RESULTS: Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. CONCLUSION: PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

STUDY DESIGN: Case report. OBJECTIVE: Diagnosis of symptomatic extra-foraminal lumbosacral stenosis using diffusion tensor imaging (DTI). SUMMARY OF BACKGROUND DATA: Conventional magnetic resonance imaging (MRI) has sometimes proved inadequate for evaluating symptomatic spinal nerve lesions. DTI has been developed to visualize anisotropy of nerve-fiber tracts to evaluate nerve degeneration. We report a case of nerve compression causing a far-out lesion diagnosed using DTI. METHODS: A 68-year-old patient presented with an 8-month history of severe right-sided sciatica. Computed tomography and MRI showed right L5-S1 foraminal stenosis and contact of the L5 transverse process and S1 ala without canal stenosis at the L4-L5 level. We evaluated the fractional anisotropy (FA) of the right L5 spinal nerve and compared it with bilateral L3-S1 spinal nerves to determine the L5 spinal nerve compression site. RESULTS: DTI revealed narrowing of the right L5 spinal nerve between the L5 transverse process and S1 ala. FA was significantly decreased in the right L5 spinal nerve between the L5 transverse process and S1 ala. There was no significant difference in the FA of spinal nerves between the right and left sides at L3, L4, or S1. The right L5 spinal nerve from the central spinal canal to the extra-foraminal lumbosacral lesion was exposed during surgery and found to be severely compressed by the L5 transverse process and S1 ala. Postoperatively, the patient's symptoms disappeared immediately. CONCLUSION: We used DTI to diagnose a symptomatic lesion as an extra-foraminal lumbosacral lesion caused by compression of the L5 spinal nerve at the foramina. Because DTI can quantitatively measure damage to nerve fibers, it may be advantageous for the diagnosis of far-out syndrome.