Effectiveness of a report writing training program using peer review: evidence from first- year medical students.

BACKGROUND: Report writing in class provides basic training for academic writing. However, report writing education in medical schools in Japan has rarely been reported and no teaching strategy has been established for it. METHODS: This study developed a report writing program using peer review for first-year medical students consisting of two 120-minute classes. The goal of being able to write reports appropriately was established and presented to students at the beginning of the program. In session 1, students decided on a topic, gathered information, and structured their report. In session 2, students' written reports were peer reviewed. The reports were improved based on the peer reviews. The responses of the pre- and post-program questionnaires were evaluated to determine the program's effectiveness. The other reports that were assigned one month after the program were used as comparison with the reports of students who did not participate. Furthermore, the long-term effects of the program were also evaluated by comparing the results of students from the previous year who did not participate in the program with those of program participants six months after the program. RESULTS: A total of 106 students completed the questionnaire evaluation. The program was rated as being acceptable for the students. Self-assessment of report writing significantly improved after the program. The report scores of program participants (n = 99) were significantly higher overall and in all domains than were those of non-participants (n = 99). The self-assessment of students who participated (n = 96) was significantly higher than that of non-participants (n = 109). No difference was observed for students' sense of burden in report writing. CONCLUSIONS: The report writing skills of medical students can be improved by clearly establishing the goals of report writing and practicing the basic skills of report writing step-by-step. Moreover, the use of peer review may enhance the effectiveness of learning opportunities for report writing.

Influencing physician distribution through education: a qualitative study on retention in Japan's rural hospitals.

BACKGROUND: Addressing the shortage of healthcare professionals in rural Japan poses significant challenges. At Sanmu Medical Center, incorporating resident physicians into a general medicine training program has proved effective in retaining them as supervising physicians. This study aims to identify the key factors contributing to the success of such programs. METHODS: We used a qualitative research design to comprehensively understand the factors contributing to physician retention in regional community hospitals in areas with physician shortages. Interviews were conducted with four experienced physicians, including the center director, who participated in the general or family medicine training programs at Sanmu Medical Center. Using a semi-structured questionnaire, we explored the factors influencing physician retention in community-based hospitals experiencing shortages. Two physicians specializing in community medicine conducted a content analysis under the supervision of three experts in community-oriented medical education and qualitative research. This approach helped compare retention factors perceived by physicians and the center director. RESULTS: Content analysis revealed 10 categories and 47 subcategories. The analysis revealed that "Educational activity" and "Supervising physicians and guidance system" are crucial for physician retention in rural hospitals in Japan. The study highlighted key educational factors contributing to retention: engagement in educational activities led to personal and professional growth, creating a rewarding experience for the physicians. Furthermore, a structured supervising physician system provided essential guidance and mentorship, improving the educational environment. Diverse learning opportunities and protected learning times were identified as critical for fostering a sustainable commitment among physicians to work in rural settings. These findings contribute to existing literature by detailing how structured educational activities and mentorship programs in rural hospital settings can significantly impact physician retention. CONCLUSIONS: Community-based medical education programs that focus on diverse clinical settings, mentorship, and a supportive work environment can enhance physician retention in rural areas. By fostering such educational and professional environments, healthcare institutions can address physician maldistribution and improve care quality in underserved communities. Our study offers practical insights that can be replicated or adapted by other rural hospitals facing similar challenges. It offers targeted strategies to address the unique challenges faced by female physicians in rural healthcare settings.

Impact of group work on the hidden curriculum that induces students' unprofessional behavior toward faculty.

BACKGROUND: Hidden curriculum (HC) can limit the effects of professionalism education. However, the research on how HC triggers unprofessional behavior among medical students is scant. Furthermore, there is no established approach for how faculty members may create a context, such as an educational environment and education system, that prevents students' unprofessional behavior. This study aimed to develop an educational approach to prevent unprofessional behavior and clarify how faculty members consider HC that triggers students' unprofessional behavior. METHODS: The study sample comprised 44 faculty members and eight medical students from the Chiba University School of Medicine. The participants were divided into groups and asked the following question: "What attitudes, statements, and behaviors of senior students, physicians, and faculty members trigger medical students' unprofessional behavior?" The responses were collected using the affinity diagram method. The group members discussed the causes and countermeasures for the selected attitudes, statements, and behaviors of senior students, physicians, and faculty members based on the affinity diagram. The impact of the group work on the faculty members was surveyed using questionnaires immediately after its completion and six months later. Furthermore, the cards in the group work were analyzed using content analysis. RESULTS: The responses to the questionnaire on group work indicated that some faculty members (43.8%) improved HC, while others suggested conducting group work with more participants. The content analysis revealed six categories - inappropriate attitude/behavior, behavior encouraging unprofessional behavior, lack of compliance with regulations, harassment of other medical staff, inappropriate educational environment/supervisor, and inappropriate self-control - and 46 subcategories. CONCLUSIONS: The HC that triggers students' unprofessional behavior includes the words and actions of the educator, organizational culture, and educational environment. Group work makes faculty members aware of the HC that triggers unprofessional behavior, and induces behavioral change for HC improvement in the educational activities. Educators should refrain from using words and actions that encourage unprofessional behavior, such as personal anecdotes, as they reduce students' learning motivation.

The influence of Gamification on medical students' diagnostic decision making and awareness of medical cost: a mixed-method study.

BACKGROUND: The gamification of learning increases student enjoyment, and motivation and engagement in learning tasks. This study investigated the effects of gamification using decision-making cards (DMCs) on diagnostic decision-making and cost using case scenarios. METHOD: Thirty medical students in clinical clerkship participated and were randomly assigned to 14 small groups of 2-3 medical students each. Decision-making was gamified using DMCs with a clinical information heading and medical cost on the front, and clinical information details on the back. First, each team was provided with brief clinical information on case scenarios. Subsequently, DMCs depending on the case were distributed to each team, and team members chose cards one at a time until they reached a diagnosis of the case. The total medical cost was then scored based on the number and contents of cards drawn. Four case scenarios were conducted. The quantitative outcomes including confidence in effective clinical decision-making, motivation to learn diagnostic decision-making, and awareness of medical costs were measured before and after our gamification by self-evaluation using a 7-point Likert scale. The qualitative component consisted of a content analysis on the benefits of learning clinical reasoning using DMCs. RESULT: Confidence in effective clinical decision-making, motivation to learn diagnostic decision-making, and awareness of medical cost were significantly higher after the gamification. Furthermore, comparing the clinical case scenario tackled last with the one tackled first, the average medical cost of all cards drawn by students decreased significantly from 11,921 to 8,895 Japanese yen. In the content analysis, seven advantage categories of DMCs corresponding to clinical reasoning components were extracted (information gathering, hypothesis generation, problem representation, differential diagnosis, leading or working diagnosis, diagnostic justification, and management and treatment). CONCLUSION: Teaching medical students clinical reasoning using DMCs can improve clinical decision-making confidence and learning motivation, and reduces medical cost in clinical case scenarios. In addition, it can help students to acquire practical knowledge, deepens their understanding of clinical reasoning, and identifies several important clinical reasoning skills including diagnostic decision-making and awareness of medical costs. Gamification using DMCs can be an effective teaching method for improving medical students' diagnostic decision-making and reducing costs.

How long will it take to reach the gender diversity goal for orthopaedics in Japan?

BACKGROUND: In Japan, orthopaedics is one of the medical fields with the lowest proportion of women. This study analyses the change in gender diversity over the past decade and estimates the time required to achieve the 30% gender diversity goal, according to the critical mass in Japan in 2020. METHODS: We investigated the demographic composition of orthopaedic surgeons in 2020 by age group, the gender ratio of the main clinical fields from 2010 to 2020, and estimated the time required for the bottom 10 (i.e., least diverse) medical departments in Japan to reach the proportion of 30% women. We used simple linear regression analyses to clarify the number of years. RESULTS: In 2020, the population pyramid of orthopaedic surgeons showed that those in their 50s were the largest component with 24.1%, followed by those in their 40s and 30s with 22.3% and 19.4%, respectively. The percentage of women orthopaedic surgeons increased slightly from 4.1% in 2010 to 5.7% in 2020. This means that to achieve the proportion of 30% women at the current annual increase rate, orthopaedics would require up to 160 years, cardiovascular 149 years, and neurosurgery 135 years. CONCLUSION: Contrary to the recent increase in the number of women physicians, there has been only a slight increase in the number of women orthopaedic surgeons over the past decade. Moreover, the number of young male orthopaedic surgeons has decreased. As current orthopaedic surgeons age and retire, Japan will soon face an overall shortage of orthopaedic surgeons. Issues that must still be addressed in Japanese orthopaedics include educating men and women about gender diversity and bias, changing stereotypes about surgical lifestyles, improving work-life balance, and diligent and collaborative efforts at both the individual and community levels.

Using peer role-playing to improve students' clinical skills for musculoskeletal physical examinations.

BACKGROUND: The traditional curriculum for medical students in Japan does not include sufficient opportunities for students to develop their skills for musculoskeletal (MSK) examination and clinical reasoning and diagnosis. Therefore, an effective programme is required to help medical students and residents improve their clinical skills in MSK. This paper aims to assess the clinical skills of medical students who have participated in a peer role-playing simulation programme using a mini clinical evaluation exercise (mini-CEX). METHODS: Participants were 90 female medical students who were completing their first orthopaedic clinical clerkship. They were divided into two groups. The simulation group participated in a role-play focussed on MSK cases as low-fidelity simulation, a structured debriefing with the course supervisor, and a self-reflection on Day 1 (n = 64). The control group did not participate in the role-play due to randomised clerkship schedules (n = 26). On Day 2 of the intervention, we observed and assessed all participants' performances during MSK outpatient encounters using the mini-CEX. We compared the mini-CEX score between the simulation group and the control group; the Wilcoxon rank-sum test was used for statistical analysis. RESULTS: The mini-CEX scores for physical examination, clinical reasoning and diagnosis, and overall clinical competency were significantly higher in the simulation group than in the control group (p < .05, physical examination: p = .014, clinical reasoning: p = .042, overall: p = .016). These findings suggest that medical students who partake in a peer role-playing simulation programme could experience improved clinical skills for physical examination, clinical reasoning and diagnosis, and overall clinical competency in real-life MSK outpatient encounters. CONCLUSIONS: Through a mini-CEX assessment, our findings indicate that medical students who participated in our peer role-playing simulation programme have improved clinical skills. Peer role-playing as a low-fidelity simulation and practical educational opportunity will enable educators to polish the competency of medical students in musculoskeletal physical examinations and clinical reasoning and diagnosis in a clinical setting.

Pentosidine concentration is associated with degenerative lumbar scoliosis in older women: preliminary results.

PURPOSE: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. The objective of the study was to investigate the prevalence of sarcopenia in degenerative lumbar scoliosis (DLS), and the relationship between biochemical markers including major AGEs, pentosidine, and DLS in older women. METHODS: Our study participants were 20 elderly women with idiopathic DLS (mean age 76.4 years, range 56-88). Nineteen age- and sex-matched volunteers (mean age 74.0 years, range 62-86) served as controls. Spinal and femoral BMD of all participants was measured using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index [SMI; appendicular lean mass (kg)/(height (m)]2. SMI < 5.75 was considered diagnostic for sarcopenia. Coronal and sagittal spinal alignments were measured. The following biochemical markers were measured: serum and urinary pentosidine, serum homocysteine, 1,25(OA)2D, and 25(OH)D. The level of each variable was compared between DLS and controls. The relationship between biochemical markers including pentosidine and DLS was examined. RESULTS: Sarcopenia was observed at a high prevalence in participants with DLS: 50% compared with 15.8% of healthy controls. Height, weight, femoral BMI, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DLS group. Serum pentosidine was significantly higher for the DLS group compared with controls. Correlations with serum pentosidine revealed a significant positive correlation between lumbar scoliosis, pelvic tilt, and pelvic incidence-lumbar lordosis mismatch, and a significantly negative correlation between thoracic kyphosis (P < 0.05). CONCLUSIONS: We found that sarcopenia was involved in DLS, and high serum pentosidine levels are associated with severity of coronal and sagittal malalignment in older women, suggesting that high levels of AGEs are a potential biomarker for the progression of lumbar scoliosis and kyphotic deformity. Further studies are needed to clarify the pathogenesis of DLS.

Anatomical evaluation of lumbar nerves using diffusion tensor imaging and implications of lateral decubitus for lateral transpsoas approach.

PURPOSE: Recently, lateral interbody fusion (LIF) has become more prevalent, and evaluation of lumbar nerves has taken on new importance. We report on the assessment of anatomical relationships between lumbar nerves and vertebral bodies using diffusion tensor imaging (DTI). METHODS: Fifty patients with degenerative lumbar disease and ten healthy subjects underwent DTI. In patients with lumbar degenerative disease, we studied nerve courses with patients in the supine positions and with hips flexed. In healthy subjects, we evaluated nerve courses in three different positions: supine with hips flexed (the standard position for MRI); supine with hips extended; and the right lateral decubitus position with hips flexed. In conjunction with tractography from L3 to L5 using T2-weighted sagittal imaging, the vertebral body anteroposterior span was divided into four equally wide zones, with six total zones defined, including an anterior and a posterior zone (zone A, zones 1-4, zone P). We used this to characterize nerve courses at disc levels L3/4, L4/5, and L5/S1. RESULTS: In patients with degenerative lumbar disease, in the supine position with hips flexed, all lumbar nerve roots were located posterior to the vertebral body centers in L3/4 and L4/5. In healthy individuals, the L3/4 nerve courses were displaced forward in hips extended compared with the standard position, whereas in the lateral decubitus position, the L4/5 and L5/S nerve courses were displaced posteriorly compared with the standard position. CONCLUSIONS: The L3/4 and L4/5 nerve roots are located posterior to the vertebral body center. These were found to be offset to the rear when the hip is flexed or the lateral decubitus position is assumed. The present study is the first to elucidate changes in the course of the lumbar nerves as this varies by position. The lateral decubitus position or the position supine with hips flexed may be useful for avoiding nerve damage in a direct lateral transpsoas approach. Preoperative DTI seems to be useful in evaluating the lumbar nerve course as it relates anatomically to the vertebral body.

Radiographic evaluation of indirect decompression of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion for degenerated lumbar spondylolisthesis.

PURPOSE: Extreme lateral interbody fusion provides minimally invasive treatment of spinal deformity, but complications including nerve and psoas muscle injury have been noted. To avoid nerve injury, mini-open anterior retroperitoneal lumbar interbody fusion methods using an approach between the aorta and psoas, such as oblique lumbar interbody fusion (OLIF) have been applied. OLIF with percutaneous pedicle screws without posterior decompression can indirectly decompress the spinal canal in lumbar degenerated spondylolisthesis. In the current study, we examined the radiographic and clinical efficacy of OLIF for lumbar degenerated spondylolisthesis. METHODS: We assessed 20 patients with lumbar degenerated spondylolisthesis who underwent OLIF and percutaneous pedicle screw fixation without posterior laminectomy. MR and CT images and clinical symptoms were evaluated before and 6 months after surgery. Cross sections of the spinal canal were evaluated with MRI, and disk height, cross-sectional areas of intervertebral foramina, and degree of upper vertebral slip were evaluated with CT. Clinical symptoms including low back pain, leg pain, and lower extremity numbness were evaluated using a visual analog scale and the Oswestry Disability Index before and 6 months after surgery. RESULTS: After surgery, significant increases in axial and sagittal spinal canal diameter (12 and 32 %), spinal canal area (19 %), disk height (61 %), and intervertebral foramen areas (21 % on the right side, 39 % on the left), and significant decrease of upper vertebral slip (-9 %) were found (P < 0.05). Low back pain, leg pain, and lower extremity numbness were significantly reduced compared with before surgery (P < 0.05). CONCLUSIONS: Significant improvements in disk height and spinal canal area were found after surgery. Bulging of disks was reduced through correction, and stretching the yellow ligament may have decompressed the spinal canal. Lumbar anterolateral fusion without laminectomy may be useful for lumbar spondylolisthesis with back and leg symptoms.

The nature of osteoporotic low back pain without acute vertebral fracture: A prospective multicenter study on the analgesic effect of monthly minodronic acid hydrate.

BACKGROUND: Patients with osteoporosis but no evidence of fracture can sometimes report low back pain. However, few studies have evaluated the nature of osteoporotic low back pain in a clinical situation. Therefore, the aim of this study was to examine the nature of osteoporotic low back pain without fracture, and the analgesic effect of minodronic acid hydrate on such pain. METHODS: The current study examined 136 patients with osteoporotic low back pain and no lower extremity symptoms. The following factors were evaluated before and after minodronic acid hydrate administration: the nature of osteoporotic low back pain was evaluated using the painDETECT questionnaire, numeric rating scale (NRS) score for low back pain at rest and in motion, bone mineral density (BMD) of the lumbar spine, and the serum concentration of tartrate-resistant acid phosphatase 5b (TRACP-5b) as a bone metabolism marker. RESULTS: A total of 113 patients were enrolled. The painDETECT questionnaire revealed the percentage of patients with nociceptive pain and neuropathic or mixed pain was approximately 85% and 15%, respectively. the average NRS scores for low back pain at rest decreased significantly 2 months after treatment (p = 0.01), while those in motion decreased significantly 1 month after treatment (p = 0.04). The average lumbar spine BMD tended to increase after treatment, but not significantly. On the other hand, the changes in the average serum concentration of TRACP-5b did significantly decrease 1 month after treatment. There was a significant positive correlation between the rate of NRS score improvement for low back pain at rest, and the rate of improvement in serum concentration of TRACP-5b (p < 0.05). CONCLUSIONS: Osteoporotic low back pain consisted of 85% nociceptive pain and 15% neuropathic or mixed pain. The pain is strongly related to pain at rest rather than that in motion.

Muscle injury in rats induces upregulation of inflammatory cytokines in injured muscle and calcitonin gene-related peptide in dorsal root ganglia innervating the injured muscle.

INTRODUCTION: In this study we evaluated the relationships among the behavioral changes after muscle injury, histological changes, changes in inflammatory cytokines in the injured muscle, and changes in the sensory nervous system innervating the muscle in rats. METHODS: We established a model of muscle injury in rats using a dropped weight. Behavior was assessed using the CatWalk system. Subsequently, bilateral gastrocnemius muscles and dorsal root ganglia (DRGs) were resected. Muscles were stained with hematoxylin and eosin, and inflammatory cytokines in injured muscles were assayed. DRGs were immunostained for calcitonin gene-related peptide (CGRP). RESULTS: Changes of behavior and upregulation of inflammatory cytokines in injured muscles subsided within 2 days of injury. Repaired tissue was observed 3 weeks after injury. However, upregulation of CGRP in DRG neurons continued for 2 weeks after injury. CONCLUSION: These findings may explain in part the pathological mechanism of persistent muscle pain. Muscle Nerve 54: 776-782, 2016.

Single Intradiscal Administration of the Tumor Necrosis Factor-Alpha Inhibitor, Etanercept, for Patients with Discogenic Low Back Pain.

OBJECTIVE: To examine the analgesic effect of intradiscal administration of a tumor necrosis factor-αα (TNF-α) inhibitor in patients with discogenic low back pain (LBP). DESIGN: Prospective, randomized study. SETTING: Department of Orthopaedic Surgery, Chiba (Japan) University Hospital. SUBJECTS: Seventy-seven patients diagnosed with discogenic LBP. METHODS: Discogenic LBP patients were randomly assigned to the etanercept (n = 38; bupivacaine [2 mL] with etanercept [10 mg]) or control (n = 39; bupivacaine [2 mL]) groups. Patients received a single intradiscal injection. Numerical rating scale (NRS) scores for LBP at baseline, 1 day, and 1, 2, 4, and 8 weeks after the injection were recorded. The Oswestry disability index (ODI) scores at baseline and at 4 and 8 weeks after injection were evaluated. Postinjection complications were recorded and evaluated. RESULTS: In the etanercept group, the NRS scores were significantly lower than in the control group at every time point after the injection for 8 weeks (P < 0.05). Similarly, 4 weeks after the injection, the ODI score was lower in the etanercept group than in the control group (P < 0.05). However, the ODI scores were not significantly different at 8 weeks. Complications were not observed. CONCLUSIONS: Single intradiscal administration of a TNF-α inhibitor can alleviate intractable discogenic LBP for up to 8 weeks. TNF-α may be involved in discogenic pain pathogenesis. This procedure is a novel potential treatment; longer-term effectiveness trials are required in the future.

Single intradiscal injection of the interleukin-6 receptor antibody tocilizumab provides short-term relief of discogenic low back pain; prospective comparative cohort study.

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.

Anti-RANKL antibodies decrease CGRP expression in dorsal root ganglion neurons innervating injured lumbar intervertebral discs in rats.

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.

The Effects of Generally Administered Anti-Nerve Growth Factor Receptor (p75NTR) Antibody on Pain-Related Behavior, Dorsal Root Ganglia, and Spinal Glia Activation in a Rat Model of Brachial Plexus Avulsion.

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.

The prevalence and characteristics of low back pain among sitting workers in a Japanese manufacturing company.

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.

A novel rat model of hip pain by intra-articular injection of nerve growth factor-characteristics of sensory innervation and inflammatory arthritis.

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.

Schwann cell LRP1 regulates remak bundle ultrastructure and axonal interactions to prevent neuropathic pain.

Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. These anatomical changes in the PNS were associated with mechanical allodynia, even in the absence of nerve injury. In response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated degeneration and Schwann cell death. Remyelinated axons were evident 20 d after crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly increased and sustained mechanical allodynia and loss of motor function. Evidence for central sensitization in pain processing included increased p38MAPK activation and activation of microglia in the spinal cord. These studies identify LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in which LRP1 is deficient in Schwann cells represent a model for studying how abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.

Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats.

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.

The effects of locally injected triamcinolone on entrapment neuropathy in a rat chronic constriction injury model.

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-1ß (IL-1ß) 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-1ß 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.