Neuropathic pain development and maintenance and its association with motor recovery after cervical spinal cord injury

In our published randomized controlled trial, we revealed that patients with acute ASIA Grade C incomplete cervical spinal cord injury (SCI) who underwent early surgery (within 24 h post-injury) had accelerated motor recovery at six months than those with delayed surgery (>2 weeks post-injury); however, neuropathic pain (NeP) worsened regardless of surgery timing. Here, we conducted post-hoc analyses to intensively assess NeP development and maintenance. Of 44 patients (median 64.5 years; three female; early intervention, n = 26), NeP was categorized into at-level and below-level pain and evaluated at  two weeks and one year after injury using the Neuropathic Pain Symptom Inventory (NPSI). We compared the two groups based on background characteristics. A mixed-design analysis of variance with sex as a covariate was conducted to analyze motor recovery and Health-related quality of life (HRQOL) in groups with severe (NPSI ≥ 10) or mild (NPSI  Upper and lower limb motor impairments were comparable between both groups regardless of pain severity. Severe at-level pain remained stable and worsened at one year than mild at-level pain; however, the upper- and lower-limb motor scores and HRQOL had comparable recovery. Background characteristics did not affect severity or time course of NeP. Patients with severe below-level pain demonstrated slower lower-limb motor recovery than those with mild below-level pain, whereas HRQOL improved regardless of pain severity. Both at-level and below-level NeP developed and persisted relatively early in the course of traumatic SCI with incomplete motor paralysis; their severities worsened over time or remained severe since onset.</p

Annual trends in the proportion of meniscectomy and meniscus repair categorized by age.

<p>The Japanese academic year begins April 1 and ends March 31. (A) < 30 years old. (B) 30–59 years old. (C) ≥ 60 years old.</p

Annual trends in meniscectomy and meniscus repair categorized by age.

<p>Annual trends in meniscectomy and meniscus repair categorized by age.</p

Annual trends in the proportion of meniscectomy and meniscus repair from 2007 to 2014.

<p>The Japanese academic year begins April 1 and ends March 31.</p

Annual trends in meniscectomy and meniscus repair categorized by injured compartment.

<p>Annual trends in meniscectomy and meniscus repair categorized by injured compartment.</p

Genetic and pharmacological rescue of cleidocranial dysplasia by suppressing GSK-3β.

<p>(A) Calvarias and clavicles of <i>Gsk-3</i>β^+/+, <i>Gsk-3</i>β^+/–, <i>Runx2</i>^+/–, and <i>Gsk-3</i>β^+/–<i>; Runx2</i>^+/– neonates (0-day) stained with Alizarin red and Alcian blue (bars, 3 mm for calvaria and 0.5 mm for clavicle). (B) Quantitative analyses using the NIH image of the anterior fontanelle area and the clavicle length of the four genotypes. (C) Plain radiographs at 3 weeks of age of the skulls and clavicles of <i>Gsk-3</i>β^+/+ with and without LiCl administration from E7.5 to 3 weeks after birth, <i>Runx2</i>^+/– with and without the LiCl administration, and <i>Gsk-3</i>β^+/–<i>; Runx2</i>^+/– mice. (D) Quantitative analyses using the NIH image of the five groups. For (B) and (D), data are mean (bars)±SEM (error bars) of the relative amount compared to <i>Runx2</i>^+/– of 6 mice per group. *<i>P<</i>0.01, significant rescue by genetic GSK-3β insufficiency or LiCl.</p

Suppression of bone formation by GSK-3β in cultured osteoblasts.

<p>(A) Expressions of GSK-3β and GSK-3α in calvarial osteoblasts of <i>Gsk-3</i>β^+/+ and <i>Gsk-3</i>β^+/– littermates determined by immunoblot analysis with β-actin as a loading control. (B) Cell proliferation determined by the XTT assay in osteoblasts during 8 days of culture. Data are the mean (symbols)±SEM (error bars) of 6 dishes/genotype. (C) ALP (top), Alizarin red (middle), and von Kossa (bottom) stainings in osteoblasts cultured for 2 weeks. (D) mRNA levels of type I collagen (Col I), osteopontin, ALP, osteocalcin, Twist-1 and Twist-2, determined by real-time RT-PCR analysis in osteoblasts cultured for 2 weeks. Data are mean (bars)±SEM (error bars) of the relative amount compared to that of the <i>Gsk-3</i>β^+/+ culture 6 wells per genotype. *<i>P<</i>0.01 vs. <i>Gsk-3</i>β^+/+. (E) von Kossa staining (top) and osteocalcin mRNA level determined by real-time RT-PCR analysis (bottom) of osteoblasts transfected with the adenovirus expressing GFP, wild-type GSK-3β, constitutively active GSK-3β (CA-GSK-3β), or kinase-inactive GSK-3β (KI-GSK-3β), and cultured for 2 weeks. (F) von Kossa staining (top) and osteocalcin mRNA level (bottom) of osteoblasts cultured with and without lithium chloride (LiCl, 16 mM) or SB216763 (10 µM) for 2 weeks. For (E) and (F), the mRNA levels are mean (bars)±SEM (error bars) of the relative amount of mRNA compared to that of the control <i>Gsk-3</i>β^+/+ culture of 6 wells per group. *<i>P<</i>0.01, significant stimulation by the genetic GSK-3β insufficiency. #<i>P<</i>0.01, significant effects by the adenoviral overexpression or the GSK-3β inhibitors.</p

Additional file 1: of Development of the Japanese Core Outcome Measures Index (COMI): cross-cultural adaptation and psychometric validation

Japanese version of the Core Outcome Measures Index. Japanese version of the Core Outcome Measures Index in Japanese. (PDF 232 kb

Comparison of the Japanese Orthopaedic Association (JOA) Score and Modified JOA (mJOA) Score for the Assessment of Cervical Myelopathy: A Multicenter Observational Study

<div><p>Objectives</p><p>The Japanese Orthopaedic Association (JOA) score is widely used to assess the severity of clinical symptoms in patients with cervical compressive myelopathy, particularly in East Asian countries. In contrast, modified versions of the JOA score are currently accepted as the standard tool for assessment in Western countries. The objective of the present study is to compare these scales and clarify their differences and interchangeability and verify their validity by comparing them to other outcome measures.</p><p>Materials and Methods</p><p>Five institutions participated in this prospective multicenter observational study. The JOA and modified JOA (mJOA) proposed by Benzel were recorded preoperatively and at three months postoperatively in patients with cervical compressive myelopathy who underwent decompression surgery. Patient reported outcome (PRO) measures, including Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), the Short Form-12 (SF-12) and the Neck Disability Index (NDI), were also recorded. The preoperative JOA score and mJOA score were compared to each other and the PRO values. A Bland-Altman analysis was performed to investigate their limits of agreement.</p><p>Results</p><p>A total of ninety-two patients were included. The correlation coefficient (Spearman’s rho) between the JOA and mJOA was 0.87. In contrast, the correlations between JOA/mJOA and the other PRO values were moderate (|rho| = 0.03 – 0.51). The correlation coefficient of the recovery rate between the JOA and mJOA was 0.75. The Bland-Altman analyses showed that limits of agreement were 3.6 to -1.2 for the total score, and 55.1% to -68.8% for the recovery rates.</p><p>Conclusions</p><p>In the present study, the JOA score and the mJOA score showed good correlation with each other in terms of their total scores and recovery rates. Previous studies using the JOA can be interpreted based on the mJOA; however it is not ideal to use them interchangeably. The validity of both scores was demonstrated by comparing these values to the PRO values.</p></div

A Bland–Altman plot comparing the JOA and mJOA scores.

<p>The bias is shown as a solid line, and the upper and lower limits of agreement are shown as broken lines.</p