Deficits in the thalamocortical pathway associated with hypersensitivity to pain in patients with frozen shoulder.

Background and purpose: Frozen shoulder (FS) is a chronic pain condition and has been shown to be associated with pain sensitization. However, the underyling brain mechanisms remain unclear. Here, we aimed to explore brain alterations and their association with pain sensitization in patients with FS. Materials and methods: A total of 54 FS patients and 52 healthy controls (HCs) were included in this study. Here, we applied both structural and functional magnetic resonance imaging (MRI) techniques to investigate brain abnormalities in FS patients. Voxel-wise comparisons were performed to reveal the differences in the gray matter volume (GMV) and amplitude of low-frequency fluctuation (ALFF) between FS patients and HCs. Furthermore, the region of interest (ROI) to whole-brain functional connectivity (FC) was calculated and compared between groups. Finally, Pearson's correlation coefficients were computed to reveal the association between clinical data and brain alterations. Results: Four main findings were observed: (1) FS patients exhibited decreased thalamus GMV, which correlated with pain intensity and pain threshold; (2) relative to HCs, FS patients exhibited a higher level of ALFF within the anterior cingulate cortex (ACC) and the thalamus; (3) FS patients exhibited a significant increase in Tha-S1 FC compared to HCs; and (4) the effect of thalamus GMV on pain intensity was mediated by pain threshold in FS patients. Conclusion: The dysfunctional thalamus might induce pain hypersensitivity, which further aggravates the pain in FS patients.

Preoperative Modic changes are related to axial symptoms after anterior cervical discectomy and fusion.

BACKGROUND: The objective of this study was to compare the clinical and radiological outcomes between patients with or without axial symptoms (AS) and investigate the risk factors associated with AS by multivariate regression analysis in anterior cervical discectomy and fusion (ACDF). MATERIALS AND METHODS: The records of 117 patients who underwent ACDF were reviewed for clinical and radiological outcomes. These outcomes were evaluated before and after surgery and at the last follow-up. Preoperative Modic changes (MCs) adjacent to the treated disc were identified. Risk factors for AS were detected through logistic regression analysis. RESULTS: The patients were divided into two groups: one with AS (AS group, n=35) and the other without (NAS group, n=82). Visual Analog Scale values after the operation (P=0.013) and at final follow-up (P<0.001) and preoperative segmental angle (P=0.031) were significantly different between the two groups. There were no significant differences with respect to other clinical and radiographic outcomes between the two groups (P>0.05). Logistic regression analysis revealed that preoperative segmental kyphosis (OR =2.912, P=0.035) and MCs (odds ratio =3.268, P=0.015) were the risk factors for the occurrence of AS. CONCLUSION: AS do not correlate with recovery of neural function in patients treated by ACDF. In addition, preoperative segmental kyphosis and MCs at the fusion segment were found to affect the incidence of AS after ACDF.

miR-342-3p promotes osteogenic differentiation via targeting ATF3.

Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR-342-3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR-342-3p impairs osteoblast activity and matrix mineralization, while over expression of miR-342-3p promotes osteoblast differentiation significantly. Moreover, miR-342-3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro-osteogenic differentiation-associated genes. In addition, there exists a higher frequency of methylation at the CpG island of the Enah/Vasp-Like (EVL) locus in undifferentiated pre-osteoblasts; however, demethylation of the EVL CpG island induces over expression of miR-342-3p during osteogenic differentiation. This study suggests that miR-342-3p may serves as a potential marker for diagnosis and treatment of ossification of ligament and osteoporosis.

A Transcriptome-Level Study Identifies Changing Expression Profiles for Ossification of the Ligamentum Flavum of the Spine.

Ossification of the ligamentum flavum (OLF) is a common spinal disorder that causes myelopathy and radiculopathy. Non-coding RNAs (ncRNAs) are involved in numerous pathological processes; however, very few ncRNAs have been identified to be correlated with OLF. Here we compared the expression of lncRNA, mRNA, circRNA, and microRNA in OLF tissues from OLF patients and healthy volunteers through mRNA, lncRNA, and circRNA microarrays and microRNA sequencing. A total of 2,054 mRNAs, 2,567 lncRNAs, 627 circRNAs, and 28 microRNAs (miRNAs) were altered during the process of OLF. qPCR confirmed the differential expression of selected mRNAs and ncRNAs. An lncRNA-mRNA co-expression network, miRNA-mRNA target prediction network, and competing endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA were constructed based on a correlation analysis of the differentially expressed RNA transcripts. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the differentially expressed mRNAs and the predicted miRNAs target genes were performed. In addition, a deregulated miRNA-19b-3p-based miRNA-circRNA-lncRNA-mRNA network was confirmed, by gain-of-function and loss-of-function experiments, to function in the process of ossification. Taken together, this study provides a systematic perspective on the potential function of ncRNAs in the pathogenesis of OLF.

The analgesic effect of intravenous methylprednisolone on acute neuropathic pain with allodynia due to central cord syndrome: a retrospective study.

BACKGROUND: Central cord syndrome (CCS) may be associated with severe neuropathic pain that often resists to conventional pain therapy regimens and affects the patients' quality of life (QoL) seriously. Current treatments for CCS-associated neuropathic pain have limited evidence of efficacy. This retrospective study was performed to present the effects of early treatment with methylprednisolone (MP) on acute neuropathic pain relief and the QoL in CCS patients. PATIENTS AND METHODS: Data were collected from the medical records of CCS patients who suffered from acute neuropathic pain with allodynia. All the patients received intravenous MP treatment for up to 1 week. Patients were evaluated with standard measures of efficacy: neuropathic pain intensity, the area of allodynia, and the QoL at baseline, daily treatment, and at 1 and 3 months after the end of MP treatment. RESULTS: Thirty-four eligible patients were enrolled in our study. By the end of MP treatment, the proportion of patients who gained total or major (visual analog scale [VAS] score decreased by 50% or more) allodynia relief from the treatment was 91.18%, and a decrease in spontaneous pain was also observed. Moreover, this study showed MP could significantly improve the QoL of patients based on McGill Pain Questionnaire Short Form and EuroQol Five Dimensions Questionnaire. Four patients (11.76%) during MP treatment experienced mild or moderate side effects. None of the patients manifested CCS-associated neuropathic pain recurrence and MP-associated side effects at follow-up. CONCLUSION: The current results suggested that MP offered an effective therapeutic alternative for relieving CCS-associated acute neuropathic pain with allodynia. Given the encouraging results of this study, it would be worthwhile to confirm these results in randomized placebo-controlled clinical trials.

Clinical efficacy of calcitonin compared to diclofenac sodium in chronic nonspecific low back pain with type I Modic changes: a retrospective study.

BACKGROUND: The objective of this study was to compare the efficacy of calcitonin with diclofenac sodium in the treatment of patients with nonspecific low back pain (LBP) and type I Modic changes (MC1). PATIENTS AND METHODS: The study was a retrospective observational study with 109 patients who had nonspecific LBP and MC1 that appeared as bone marrow lesions on magnetic resonance imaging (MRI). Between October 2013 and March 2016, 62 patients were injected intramuscularly with calcitonin 50 IU once daily and 47 patients were treated with diclofenac 75 mg once per day for 4 weeks for the treatment of LBP associated with MC1 on MRI. Visual analog scale (VAS) (0-10) and Oswestry Disability Index (ODI) (0-100) questionnaires were acquired from clinical records to evaluate LBP perception and degree of disability. Imaging data were also collected before and after treatment. RESULTS: Significant improvements were found in VAS and ODI at posttreatment compared with baseline in both groups (P < 0.05). Meanwhile, there was a significant difference between calcitonin group and diclofenac group at both 4 weeks and 3 months of follow-up (4 weeks: VAS 4.46 ± 1.58 vs 5.08 ± 1.50, ODI 20.32 ± 9.64 vs 24.35 ± 7.95; 3 months: VAS 3.70 ± 1.74 vs 4.51 ± 1.67, ODI 16.67 ± 9.04 vs 21.18 ± 9.56; P < 0.05 for all). Moreover, the proportion of patients with a significant change in LBP scales was higher in the calcitonin group (4 weeks: VAS 50.00% vs 23.40%, ODI 54.83% vs 25.53%; 3 months: VAS 58.06% vs 38.29%, ODI 59.67% vs 38.29%; P < 0.05 for all). According to MRI, 43.54% patients in the calcitonin group showed improvement compared with 21.27% patients in the diclofenac group (P < 0.05). CONCLUSION: There was greater short-term efficacy of calcitonin compared with diclofenac in patients with LBP and MC1 on MRI.