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Hevin/Sparcl1 is an astrocyte-secreted protein and regulates synapse formation. Here we show that astrocytic hevin signaling plays a critical role in maintaining chronic pain. Compared to wild-type mice, hevin-null mice exhibited normal mechanical and heat sensitivity but reduced inflammatory pain. Interestingly, hevin-null mice have faster recovery than wild-type mice from neuropathic pain after nerve injury. Intrathecal injection of wild-type hevin was sufficient to induce persistent mechanical allodynia in naïve mice. In hevin-null mice with nerve injury, AAV-mediated re-expression of hevin in GFAP-expressing spinal cord astrocytes could reinstate neuropathic pain. Mechanistically, hevin is crucial for spinal cord NMDA receptor (NMDAR) signaling. Hevin potentiated NMDA currents mediated by the GluN2B-containing NMDARs. Furthermore, intrathecal injection of a neutralizing antibody against hevin alleviated acute and persistent inflammatory pain, postoperative pain, and neuropathic pain. Secreted hevin was detected in mouse cerebrospinal fluid (CSF) and nerve injury significantly increased CSF hevin abundance. Finally, neurosurgery caused rapid and substantial increases in SPARCL1/HEVIN levels in human CSF. Collectively, our findings support a critical role of hevin and astrocytes in the maintenance of chronic pain. Neutralizing of secreted hevin with monoclonal antibody may provide a new therapeutic strategy for treating acute and chronic pain and NMDAR-medicated neurodegeneration.

The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3).

To determine whether levels of pre-operative pain as recalled by a patient in the post-operative phase are possibly overestimated or underestimated compared to prospectively scored pain levels. If so, a subsequent misclassification may induce recall bias that may lead to an erroneous effect outcome.

Chronic pain is frequently comorbid with depression. However, the mechanisms underlying chronic pain-induced depression remain unclear. Here, we found that DNA methyltransferase 1 (DNMT1) was upregulated in the central amygdala (CeA) of spared nerve injury (SNI)-induced chronic pain-depression rats, and knockdown of DNMT1 could improve the depression-like behaviors in SNI rats. Additionally, a panel of differentially expressed lncRNAs, including 38 upregulated and 12 downregulated lncRNAs, were identified by microarray analysis. Bioinformatics analysis suggested that the upregulated lncRNA XR_351665 was the upstream molecule to regulate DNMT1 expression. The knockdown of XR_351665 significantly alleviated the depression-like behaviors in SNI rats, whereas overexpression of XR_351665 induced the depression-like behaviors in naïve rats. Further mechanism-related researches uncovered that XR_351665 functioned as a competing endogenous RNA (ceRNA) to upregulate DNMT1 by competitively sponging miR-152-3p, and subsequently promoted the development of chronic pain-induced depression. Our findings suggest that lncRNA XR_351665 is involved in the development of chronic pain-induced depression by upregulating DNMT1 via sponging miR-152-3p. These data provide novel insight into understanding the pathogenesis of chronic pain-induced depression and identify a potential therapeutic target.

Iliopsoas tendinopathy is a cause of groin pain following total hip arthroplasty (THA). With the anterior approach becoming increasingly popular, our aim was to determine the prevalence of iliopsoas tendinopathy following anterior approach THA, to identify risk factors, and to determine influence on patient reported outcome.

Diclofenac sodium is an anti-inflammatory drug commonly used to cure pain in various treatments. The remarkable potential of this pain-killer leads to its excessive use and, therefore, a persistent water contaminant. Its presence in aqueous bodies is hazardous for both humans and the environment because it causes the growth of harmful drug-resistant bacteria in water. Herein, we present a comparative study of the ZnO and ZnFeO as photocatalysts for the degradation of diclofenac sodium, along with their structural and morphological studies. A simple co-precipitation method was used for the synthesis of ZnO and ZnFeO and characterized by various analytical techniques. For instance, the UV-Vis study revealed the absorption maxima of ZnO at 320 nm, which was shifted to a longer wavelength region at 365 nm for zinc ferrite. The optical band gaps obtained from the Tauc plot indicated that the incorporation of iron has led to a decreased band gap of zinc ferrite (2.89 eV) than pure ZnO (3.14 eV). The metal-oxygen linkages shown by FTIR indicated the formation of desired ZnO and ZnFeO, which was further confirmed by XRD. It elucidated the typical hexagonal structure for ZnO and spinel cubic structure for ZnFeO with an average crystallite of 31 nm and 44 nm for ZnO and ZnFeO, respectively. The micrographs obtained by SEM showed rough spherical particles of ZnO, whereas for ZnFeO flower-like clustered particles were observed. The photocatalytic investigation against diclofenac sodium revealed the higher degradation efficiency of ZnFeO (61.4%) in only 120 min, whereas ZnO degraded only 48.9% of the drug. Moreover, zinc ferrite has shown good recyclability and was stable up to five runs of photodegradation with a small loss (3.9%) of photocatalytic activity. The comparison of two catalysts has suggested the promising role of zinc ferrite in wastewater remediation to eliminate hazardous pharmaceuticals.

 The addition of ultrasound-guided percutaneous cryoanalgesia (PCr) for pain management after pectus excavatum (PE) surgery offers a new and advantageous approach. Our aim is to describe our experience with PCr applied on the same day, 24 hours, and 48 hours prior to PE surgery.

A 37-year-old man presented with painless jaundice and pruritus. Total Bilirubin was 30-fold the upper limit of normal (ULN), while ALT and further cholestasis parameters were found to be only slightly elevated. As comprehensive diagnostics showed no abnormal findings and ruled out frequent causes of elevated cholestasis markers, we performed a liver biopsy. The biopsy revealed canalicular cholestasis with ductopenia and periportal fibrosis. Only after a further and intensive anamnesis a ligandrol-abuse could be determined as cause for the symptoms. Ligandrol is misused as a selective androgen receptor modulator to promote muscle building. This case represents a typical case of abuse of anabolic substances in amateur sports.

The membrane protein TMEM150C has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here, we examined whether expression of TMEM150C in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch, and substrate deflection, we could not evoke mechanosensitive currents in cells expressing TMEM150C. We next asked if TMEM150C is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a CRISPR/Cas9 strategy, we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c-/- mice completely lack TMEM150C protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c-/- mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c-/- mice. Since it has been claimed that TMEM150C is required for normal proprioceptor function, we made a quantitative analysis of locomotion in Tmem150c-/- mice. Here again, we found no indication that there was altered gait in Tmem150c-/- mice compared to wild-type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150C function in vivo are problematic. Furthermore, we could find no evidence that TMEM150C forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons.

A 28-year-old man with a history of tuberculous empyema and pectus excavatum visited our hospital for progressive dyspnea and leg edema. The patient had undergone an Eloesser window operation for repetitive pleuro-cutaneous fistula due to chronic tuberculous empyema in the left thorax one year prior. Chest computed tomography demonstrated severe compression of the right ventricle and inferior vena cava and chronic empyema with the Eloesser window in the left thorax. Because conservative treatment had failed, the patient underwent a total extrapleural Nuss procedure, resulting in marked relief of compression and complete resolution of leg edema and congestive hepatopathy. However, he required ventilation support due to carbon dioxide retention. Therefore, the patient underwent a modified Ravitch procedure and was weaned off ventilation support. Herein, we represent the first report of a sequential extrapleural Nuss procedure and a modified Ravitch procedure in a patient with chronic tuberculous empyema with an Eloesser window.