A Proof-of-Concept Study on the Effects of STA363 on Low Back Pain in Patients with Degenerative Disc Disease

BackgroundAlthough lumbar spinal stenosis (LSS) often coexists with other degenerative conditions, few studies have fully assessed possible contributing factors for low back pain (LBP) in patients with LSS. The purpose of this study was to identify factors associated with the severity of LBP in patients with LSS.MethodsThe patients with neurogenic claudication caused by LSS, which was confirmed by magnetic resonance imaging (MRI) were included in this cross-sectional study. Data included ratings of LBP, buttock and leg pain, and numbness on a numerical rating scale (NRS), 36-item Short-Form Survey (SF-36) scores, muscle mass measured by bioelectrical impedance analysis, and radiographic measurements including lumbopelvic alignment and slippage. The severity of LSS, endplate defects, Modic endplate changes, intervertebral disc degeneration, and facet joint osteoarthritis were evaluated on MRI. Spearman correlation and multivariate linear regression analyses were used to examine the factors associated with the severity of LBP (NRS score).ResultsA total of 293 patients (135 male and 158 female, average age 72.6 years) were analyzed. LBP was moderately correlated with buttock and leg pain, and buttock and leg numbness. Significant but weak correlations were observed between LBP and body mass index, appendicular and trunk muscle mass, all domains of SF-36, pelvic tilt, total number of endplate defects and Modic endplate changes, and summary score of disc degeneration grading, but not severity or number of spinal stenoses. In the multivariate regression analysis, age, female sex, trunk muscle mass, diabetes, NRS buttock and leg pain, NRS buttock and leg numbness, SF-36 vitality, pelvic tilt, and total number of endplate defects were associated with the severity of LBP.ConclusionsTrunk muscle mass, lumbopelvic alignment, and endplate defects, but not severity of stenosis are partly associated with severity of LBP, but buttock and leg pain and buttock and leg numbness have strongest relationships with LBP in patients with LSS.

The incidence of intervertebral disc (IVD) degeneration disease, caused by changes in the osmotic pressure of nucleus pulposus (NP) cells, increases with age. In general, low back pain is associated with IVD degeneration. However, the mechanism and molecular target of low back pain have not been elucidated, and there are no data suggesting specific biomarkers of low back pain. Therefore, the research aims to identify and verify the significant gene biomarkers of low back pain. The differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database, and the identification and analysis of significant gene biomarkers were also performed with various bioinformatics programs. A total of 120 patients with low back pain were recruited. Before surgery, the degree of pain was measured by the numeric rating scale (NRS), which enables comparison of the pain scores from individuals. After surgery, IVD tissues were obtained, and NP cells were isolated. The NP cells were cultured in two various osmotic media, including iso-osmotic media (293 mOsm/kg H2O) to account for the morbid environment of NP cells in IVD degeneration disease and hyper-osmotic media (450 mOsm/kg H2O) to account for the normal condition of NP cells in healthy individuals. The relative mRNA expression levels of CCL5, OPRL1, CXCL13, and SST were measured by quantitative real-time PCR in the in vitro analysis of the osmotic pressure experiments. Finally, correlation analysis and a neural network module were employed to explore the linkage between significant gene biomarkers and pain. A total of 371 DEGs were identified, including 128 downregulated genes and 243 upregulated genes. Furthermore, the four genes (CCL5, OPRL1, SST, and CXCL13) were identified as significant gene biomarkers of low back pain (P < 0.001) based on univariate linear regression, and CCL5 (odds ratio, 34.667; P = 0.003) and OPRL1 (odds ratio, 19.875; P < 0.001) were significantly related to low back pain through multivariate logistic regression. The expression of CCL5 and OPRL1 might be correlated with low back pain in patients with IVD degeneration disease caused by changes in the osmotic pressure of NP cells.

Endplate defects, not the severity of spinal stenosis, contribute to low back pain in patients with lumbar spinal stenosis

Retrospective cohort study. The aim of the present study is to investigate the coexisting lower back pain (LBP) in patients with cervical myelopathy and to evaluate changes in LBP after cervical spine surgery. Only a few studies with a small number of participants have evaluated the association between cervical myelopathy surgery and postoperative improvement in LBP. Patients who underwent primary cervical decompression surgery with or without fusion for myelopathy and completed preoperative and 1-year postoperative questionnaires were reviewed using a prospectively collected database involving 9 tertiary referral hospitals. The questionnaires included the patient-reported Japanese Orthopaedic Association (PRO-JOA) score and Numerical Rating Scales (NRS). The minimum clinically important difference (MCID) for NRS-LBP was defined as >30% improvement from baseline. Patient demographics, characteristics, and PRO-JOA score were compared between patients with and without concurrent LBP, and the contributor to achieving the MCID for LBP was analyzed using logistic regression analysis. A total of 786 consecutive patients with cervical myelopathy were included, of which 525 (67%) presented with concurrent LBP. LBP was associated with a higher body mass index ( P <0.001) and worse preoperative PRO-JOA score ( P <0.001). Among the 525 patients with concurrent LBP, the mean postoperative NRS-LBP significantly improved from 4.5±2.4 to 3.4±2.7 ( P <0.01) postoperatively, with 248 (47%) patients reaching the MCID cutoff. Patients with a PRO-JOA recovery rate >50% were more likely to achieve MCID compared with those with a recovery rate <0% (adjusted odd ratio 4.02, P <0.001). More than 50% of patients with myelopathy reported improvement in LBP after cervical spine surgery, and 47% achieved the MCID for LBP, which was positively correlated with a better PRO-JOA recovery rate. Treating cervical myelopathy in patients with concomitant LBP may be sufficient to mitigate concomitant LBP. Level III.

Disturbed muscular adaptation and changed motor strategies in recurrent low back pain patients during stair walking after experimental back-muscle fatigue

BackgroundLenke 5C (lumbar and or thoracolumbar) curve patterns lead to loss of lumbar lordosis which is associated with low back pain in later adulthood. We undertook our study to investigate if brace treatment may have an effect on low back pain and on improving the cosmetic appearance in late adolescents and adults.ObjectivesTo estimate if conservative treatment may have an effect on pain in single lumbar curvatures in late adolescent and adult patients with Adolescent Idiopathic Scoliosis (AIS) using a Gensingen Brace by Weiss (GBW).MethodWe investigated AIS patients with Lenke 5C pattern who wore a GBW prospectively. The inclusion criteria of our study were age over 15 years, Cobb angle greater than 20° before treatment and Risser 4 or 5. A verbal pain rating scale was used (no pain, mild pain, moderate pain, severe pain, very severe pain).ResultsA total of 26 patients met the inclusion criteria. The average age was 17.7 years and the average Cobb angle was 41.5°. Nineteen patients (73.1%) experienced mild or moderate chronic low back pain before treatment and seven patients (26.9%) were asymptomatic but seeking treatment for cosmetic reasons. At follow-up, a 23% correction of the curve was achieved. All previously symptomatic patients reported that they no longer experienced low back pain after having worn the brace regularly.ConclusionHigh correction bracing seems to have a positive effect on the curve and on chronic low back pain in patients with a scoliosis and a Lenke 5C curve pattern.Clinical implicationsHigh correction, pattern specific bracing with a GBW may be applied aiming at reducing structural curves and chronic low back pain in late adolescent and adult patients with AIS and with a single lumbar curvature.

The aim of this study was to compare quantitatively the difference in Surface Electromyography (sEMG) features between healthy subjects and low back pain (LBP) patients. We recruited thirty LBP patients and thirty healthy subjects. They performed maximum voluntary flexion (MVF), while sEMG data were collected from the multifidus, external oblique and transverse abdominal muscles. We used Integrated EMG (IEMG), Mean Power Frequency (MPF) of sEMG signals, and Median Frequency (MF) of sEMG signals as a base for analysis. Results showed that there were significant differences between the LBP group and the healthy group in all variables. For all explored muscles, there was a significant difference between the healthy group and the LBP group on IEMG (p<0.05). Furthermore, the mean IEMG values of the LBP group were lower than those of the healthy group. MPF and MF of the LBP group were higher than those of the healthy group. Meantime, MPF and MF of multifidus muscles of LBP individual were higher than those of healthy individual. The lower IEMG values in the LBP patients indicate that the discharge of the explored muscles in the LBP patients were lower than those in the healthy group. The higher MPF and MF could be explained by the fact that the lumbar muscles in LBP patients get fatigued and stiff easily, and the multifius muscles were more easily get fatigued than other explored muscles. Our study indicated that IEMG, MPF, MF of sEMG signals captured from the lumbar muscles could serve as a predictor of the risk of LBP patients.

Low back pain in patients with multiple sclerosis: A systematic review and the prevalence in a French multiple sclerosis population.

Prospective cohort study. To examine the relationship between low back pain after discectomy for disc herniation and Modic type 1 change. Lumbar vertebral bone marrow change is divided into Modic types. Some reports indicate that Modic type 1 is related to low back pain, but the reliability of this assertion is unclear. The current study examines changes in low back pain in patients with lumbar disc herniation and Modic type 1 change after lumbar discectomy without fusion surgery. Forty-five patients with lumbar disc herniation showing normal or Modic type 1 signals in their bone marrow were selected (mean age 35 years). All patients suffered low back and leg pain because of lumbar disc herniation, and underwent a discectomy without fusion. We evaluated change in low back pain [Visual analogue scale (VAS) score, Japanese Orthopedic Association score (JOAS), and Oswestry Disability Index (ODI)] before, 12 and 24 months after surgery. Twenty-three patients showed Modic type 1 signals and 22 patients showed normal intensity before surgery. VAS score, JOAS, and ODI were not significantly different between the normal and Modic type 1 groups. VAS score, JOAS, and ODI improved after surgery in both groups (P>0.05). Low back pain after surgery evaluated from the 3 scores was not significantly different in the 2 groups 12 or 24 months after surgery (P>0.05). Discectomy improved low back pain in patients suffering from lumbar disc herniation. Patients with or without Modic type 1 change showed a similar improvement of low back pain score. Low back pain in patients with disc herniation appears to mainly originate from disc or nerve root compression, and decompression surgery without fusion is an option for these patients, even those with Modic type 1 changes.

Efficacy of tramadol–acetaminophen tablets in low back pain patients with depression

Lumbar disc degenerative disc disease, accompanied by back pain, is a prominent health concern in society. The purpose of the study was to investigate the connection of arterial stiffness and body composition in the patients suffering low back pain with lumbar disc degenerative disorders. A comparative study was performed on 197 patients, both male and female, between the ages of 30 and 70, who were experiencing low back pain. These patients have undergone magnetic resonance imaging of the lumbosacral region to evaluate the intervertebral disc's nucleus and annulus as well as its signal intensity and height. The Pfirrmann grading method was used to determine the extent of disc degeneration. The statistical analysis revealed no significant link between overall body fat and stiffness index in disc bulging and nerve compression groups. However, the group experiencing nerve compression demonstrated a statistically significant association between visceral fat and reflection index in individuals who were overfat and obese. In addition, there was a notable correlation between PWV and the reflection index of the disc bulging groups. So, whole body fat and PWV had a different impact on disc degeneration. The PWV has a robust positive correlation with both the stiffness index and reflection index. The presence of subcutaneous fat and vascular stiffness may not have any impact on low back pain in patients with disc bulging and nerve compression. Early identification of vascular stiffness and study of body composition serve as initial measures to avoid the progression of disc degeneration.

Low back pain in patients with rheumatoid arthritis: Clinical characteristics and impact of low back pain on functional ability and health related quality of life

A retrospective study. To evaluate long-term outcome regarding low back pain (LBP) in patients treated surgically for scoliosis. Measures of long-term outcome after surgery for scoliosis have focused mainly on radiologic changes. However, subjective symptoms such as LBP after surgical treatment are of great concern to patients who undergo surgical treatment for scoliosis. Thirty-two patients treated surgically for scoliosis between 1976 and 1989 were included in this study. The mean duration of follow-up was 21.1 years. Eighteen patients had adolescent idiopathic scoliosis, 8 had congenital scoliosis, and 6 had symptomatic scoliosis. We evaluated long-term outcome by direct interview. Degree of LBP was evaluated by visual analogue scale score and Moskowitz classification in addition to clinical and radiologic evaluation. Patients were also asked to complete the SF-36 questionnaire. Mean visual analogue scale score at the latest follow-up was 21 (0-80), and 15% of patients had occasional or frequent LBP in Moskowitz classification. On the SF-36, score for bodily pain was not markedly different from that for age-matched controls. Among radiologic findings, level of distal fusion had no effect on the incidence or severity of LBP. Furthermore, preoperative Cobb angle, latest Cobb angle, and degenerative changes of subjacent segment each exhibited no correlation with degree of LBP, either. On the other hand, sagittal balance was a factor affecting LBP following scoliosis surgery. We evaluated long-term outcomes regarding LBP following scoliosis surgery. Regardless of residual back deformity, LBP was found to be no more frequent than in the normal population in Japan. Positive sagittal balance at the latest follow-up was a factor significantly contributing to LBP following scoliosis surgery.

Abdominal aortic calcification (AAC) is hypothesized to lead to ischemic pain of the lower back. This retrospective study aims to identify the relationship between AAC and lower back pain (LBP) in patients with degenerative lumbar spondylolisthesis. Lower back pain was assessed preoperatively and 2 years after surgery using the numeric analogue scale. Abdominal aortic calcification was assessed according to the Kauppila classification and was grouped into no, moderate, and severe. A multivariable regression, adjusted for age, sex, body mass index, hypertension, and smoking status, was used to assess the association between AAC and preoperative/postoperative LBP as well as change in LBP after surgery. A total of 262 patients were included in the final analysis. The multivariable logistic regression demonstrated an increased odds ratio (OR) for preoperative LBP ≥ 4 numeric analogue scale (OR = 9.49, 95% confidence interval [CI]: 2.71-40.59, P < 0.001) and postoperative LBP ≥ 4 (OR = 1.72, 95% CI: 0.92-3.21, P = 0.008) in patients with severe AAC compared with patients with no AAC. Both moderate and severe AAC were associated with reduced improvement in LBP after surgery (moderate AAC: OR = 0.44, 95% CI: 0.22-0.85, P = 0.016; severe AAC: OR = 0.41, 95% CI: 0.2-0.82, P = 0.012). This study demonstrates an independent association between AAC and LBP and reduced improvement after surgery. Evaluation of AAC could play a role in patient education and might be considered part of the differential diagnosis for LBP, although further prospective studies are needed.

The interleukin (IL)-6 biological system plays a key role in the pathogenesis of Paget disease (PD) of bone and pathological bone pain. Bone pain, particularly in the lower back region, is the most frequent symptom in patients with PD. This case-control study aimed to evaluate the relationship between the IL-6 system and low back pain (LBP) in patients with PD. We evaluated 85 patients with PD, with the disease localized in the lumbar spine, pelvis, and/or sacrum, and classified them based on the presence or absence of LBP, before and after aminobisphosphonate treatment. We also examined 32 healthy controls without LBP. Before treatment, IL-6 levels in patients with PD were higher than those in the controls, without difference between patients with or without LBP. Patients with PD with LBP (35/85) showed higher IL-6-soluble receptor (sIL-6R) and lower soluble glycoprotein (sgp) 130 levels compared with both patients with PD without LBP and controls (sIL-6R: 46.9 ± 7.4 vs 35.4 ± 8.6 vs 29.9 ± 4.2 ng/mL; sgp130: 307.2 ± 35.4 vs 341.4 ± 41.4 vs 417.1 ± 58.5 ng/mL, respectively). Paget disease remission, 6 months after treatment, is associated with LBP improvement. This phenomenon is associated with reduced sIL-6R levels and increased sgp130 levels in patients with PD with LBP at the baseline. Considering the biological properties of IL-6, sIL-6R, and sgp130, the results of the study suggest that the perception of LBP in patients with PD could be linked to an enhanced transmission of IL-6 signal in the specialized neural system activated by nociceptors.