Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model

AbstractAltered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. We generated a murine model for bone malignancy pain in which 2472 osteolytic sarcoma cells were injected into the femurs of mice. CircRNA microarray and quantitative PCR (qPCR) and revealed that circ9119 expression was repressed in the spinal cord of bone malignancy pain model mice, which is the first relay site involved in the transmission of nociceptive information to the cerebrum of mice that receive spinal analgesics for malignancy pain. Overexpression of circ9119 by plasmid injection in the model mice reduced progressive thermal hyperalgesia and mechanical hyperalgesia. Bioinformatics prediction and dual-luciferase reporter assay showed that circ9119 functions as a sponge of miR-26a, which targets the TLR3 3 ′-untranslated region. Furthermore, expression of miR-26a was elevated and TLR3 level was repressed in bone malignancy pain model mice, which were counteracted by circ9119 in the spinal cord of tumor-bearing mice. Moreover, excessive expression of miR-26a was involved in the recovery of mice from progressive thermal hyperalgesia and mechanical hyperalgesia triggered via circ9119. TLR3 knockdown in bone malignancy pain model mice thoroughly impaired pain in the initial stages and reduced the effects of circ9119 on hyperalgesia. Our research findings indicate that targeting the circ9119-miR-26 a-TLR3 axis may be...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research

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ConclusionsThe natural history of MSCC in children is associated to permanent paralysis, sensory loss, and sphincter dysfunction, thus prompt diagnosis and correct management are needed to minimize morbidity. Treatment strategies differed widely among cancer types and study groups in the absence of optimal evidence-based treatment guidelines. When the diagnosis is uncertain, surgery provides an opportunity to biopsy the lesion in addition to treating the mass.
Source: Italian Journal of Pediatrics - Category: Pediatrics Source Type: research
In conclusion, T cells infiltrated into the spinal cord with the imbalance of Th17/Treg towards Th17 during the development of BCP, which could promote the microglial activation and further increased BCP, while neutralizing IL-17/IL-17A in the spinal cord could ameliorate BCP. Our results suggest that targeting the imbalanced Th17/Treg infiltration in the spinal cord could be a novel strategy for BCP therapy.
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
In conclusion, T cells infiltrated into the spinal cord with the imbalance of Th17/Treg towards Th17 during the development of BCP, which could promote the microglial activation and further increased BCP, while neutralizing IL-17/IL-17A in the spinal cord could ameliorate BCP. Our results suggest that targeting the imbalanced Th17/Treg infiltration in the spinal cord could be a novel strategy for BCP therapy. PMID: 30685532 [PubMed - as supplied by publisher]
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
ConclusionPediatric neck pain and/or torticollis should raise high suspicion for malignancy of cervical spine. Modern diagnostic means and techniques can assist in the screening and diagnosis of these tumors.
Source: Polish Journal of Neurology and Neurosurgery - Category: Neurosurgery Source Type: research
CONCLUSION: Pediatric neck pain and/or torticollis should raise high suspicion for malignancy of cervical spine. Modern diagnostic means and techniques can assist in the screening and diagnosis of these tumors. PMID: 29544873 [PubMed - as supplied by publisher]
Source: Neurologia i Neurochirurgia Polska - Category: Neurology Authors: Tags: Neurol Neurochir Pol Source Type: research
In this study, we aimed to present 25 patients diagnosed with a spinal metastasis of unknown primary who presented with a low back pain or acute-onset neurological deficits and underwent operative treatment.
Source: World Neurosurgery - Category: Neurosurgery Authors: Source Type: research
In this study, we reviewed 25 patients diagnosed with a spinal metastasis of unknown primary who presented with low back pain or acute-onset neurologic deficits and underwent operative treatment.
Source: World Neurosurgery - Category: Neurosurgery Authors: Tags: Original Article Source Type: research
ConclusionThere is significant diversity of practice in pediatric palliative RT. Combined with ongoing research characterizing treatment response and toxicity, these data will inform the design of forthcoming clinical trials to establish effective regimens and minimize treatment toxicity for this patient population.
Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: RESEARCH ARTICLE Source Type: research
Abstract: Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translati...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
In the United States, bone tumors (Osteosarcoma and Ewing ’s sarcoma) account for nearly 800 new cases of pediatric cancer per year. These solid bone tumors typically occur in long bones and are treated with systemic chemotherapy and surgery which causes increased morbidity with long term consequences. Over the years, surgical procedures have evolved fro m amputation to limb-salvage procedures in an attempt to maintain the anatomical structures and functionality of the affected structure. Adequate pain control in the acute post-operatory setting and the recovery are a fundamental key to bringing the patient back func...
Source: The Journal of Pain - Category: Materials Science Authors: Source Type: research
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