A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression.

Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.

Effect of intrathecal NIS-lncRNA antisense oligonucleotides on neuropathic pain caused by nerve trauma, chemotherapy, or diabetes mellitus.

Background: Blocking increased expression of nerve injury-specific long non-coding RNA (NIS-lncRNA) in injured dorsal root ganglia (DRG) through DRG microinjection of NIS-lncRNA small hairpin interfering RNA or generation of NIS-lncRNA knockdown mice mitigates neuropathic pain. However, these strategies are impractical in the clinic. This study employed a Food and Drug Administration (FDA)-approved antisense oligonucleotides strategy to examine the effect of NIS-lncRNA ASOs on neuropathic pain.

A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression.

Maladaptive changes of nerve injury-associated genes in dorsal root ganglia (DRGs) are critical for neuropathic pain genesis. Emerging evidence supports the role of long noncoding RNAs (lncRNAs) in regulating gene transcription. Here we identified a conserved lncRNA, named nerve injury-specific lncRNA (NIS-lncRNA) for its upregulation in injured DRGs exclusively in response to nerve injury.

E74-like factor 1 contributes to nerve trauma-induced nociceptive hypersensitivity through transcriptionally activating matrix metalloprotein-9 in dorsal root ganglion neurons.

Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown.

A Compound Mitigates Cancer Pain and Chemotherapy-Induced Neuropathic Pain by Dually Targeting nNOS-PSD-95 Interaction and GABA Receptor.

Metastatic bone pain and chemotherapy-induced peripheral neuropathic pain are the most common clinical symptoms in cancer patients. The current clinical management of these two disorders is ineffective and/or produces severe side effects. The present study employed a dual-target compound named as ZL006-05 and examined the effect of systemic administration of ZL006-05 on RM-1-induced bone cancer pain and paclitaxel-induced neuropathic pain.

Downregulation of a Dorsal Root Ganglion-Specifically Enriched Long Noncoding RNA is Required for Neuropathic Pain by Negatively Regulating RALY-Triggered Ehmt2 Expression.

Nerve injury-induced maladaptive changes of gene expression in dorsal root ganglion (DRG) neurons contribute to neuropathic pain. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression. Here, a conserved lncRNA is reported, named DRG-specifically enriched lncRNA (DS-lncRNA) for its high expression in DRG neurons.

FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons.

Background And Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N6-methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N6-methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown.

Eukaryotic initiation factor 4 gamma 2 contributes to neuropathic pain through down-regulation of Kv1.2 and the mu opioid receptor in mouse primary sensory neurones.

Background: Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to neuropathic pain genesis. Eukaryotic initiation factor 4 gamma 2 (eIF4G2) is a general repressor of cap-dependent mRNA translation. Whether DRG eIF4G2 participates in nerve injury-induced alternations in gene expression and nociceptive hypersensitivity is unknown.

Injectable PLGA-Coated Ropivacaine Produces A Long-Lasting Analgesic Effect on Incisional Pain and Neuropathic Pain.

The management of persistent postsurgical pain and neuropathic pain remains a challenge in the clinic. Local anesthetics have been widely used as simple and effective treatment for these 2 disorders, but the duration of their analgesic effect is short. We here reported a new poly lactic-co-glycolic acid (PLGA)-coated ropivacaine that was continuously released in vitro for at least 6 days.

N-Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons.

Nerve injury-induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N-methyladenosine (mA) modification of RNA represents an additional layer of gene regulation. Here, it is reported that peripheral nerve injury increases the expression of the mA demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the gene promoter.

Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons.

Toll like receptor 7 (TLR7) is expressed in neurons of the dorsal root ganglion (DRG), but whether it contributes to neuropathic pain is elusive. We found that peripheral nerve injury caused by ligation of the fourth lumbar (L) spinal nerve (SNL) or chronic constriction injury of sciatic nerve led to a significant increase in the expression of TLR7 at mRNA and protein levels in mouse injured DRG. Blocking this increase through microinjection of the adeno-associated virus (AAV) 5 expressing TLR7 shRNA into the ipsilateral L DRG alleviated the SNL-induced mechanical, thermal and cold pain hypersensitivities in both male and female mice.

Synaptic Dynamics of the Feed-forward Inhibitory Circuitry Gating Mechanical Allodynia in Mice.

Background: The authors' previous studies have found that spinal protein kinase C γ expressing neurons are involved in the feed-forward inhibitory circuit gating mechanical allodynia in the superficial dorsal horn. The authors hypothesize that nerve injury enhances the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enables Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons.

Methods: Prkcg-P2A-tdTomato mice were constructed using the clustered regularly interspaced short palindromic repeats and clustered regularly interspaced short palindromic repeats-associated nuclease 9 technology, and were used to analyze the electrophysiologic properties of spinal protein kinase C γ expressing neurons in both normal conditions and pathologic conditions induced by chronic constriction injury of the sciatic nerve.

Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats.

Background: Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear.

Methods: We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund's adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model.

Comparisons of recurrence-free survival and overall survival between microwave versus radiofrequency ablation treatment for hepatocellular carcinoma: A multiple centers retrospective cohort study with propensity score matching.

Both microwave (MW) ablation and radiofrequency (RF) ablation are widely used for hepatocellular carcinoma (HCC) treatments in clinic. However, it is still unclear if ablative methods could influence the recurrence-free survival (RFS) and overall survival (OS) of HCC patients. Therefore, we carried out this multi-center retrospective cohort study to investigate the differences of recurrence-free survival (RFS) and overall survival (OS) between MW ablation and RF ablation by survival analysis.

High sensitive detection of circulating tumor cell by multimarker lipid magnetic nanoparticles and clinical verifications.

Tumor cells with heterogeneity and diversity can express different markers. At present, positive separation of circulating tumor cells (CTC) taking EpCAM as the marker was used in most cases which could be one-sided, while this study successfully prepared four antibody-modified magnetic immunoliposomes (MIL) by using the self-assembled liposome with antibody derivatives. This study aims to explore the separation efficiency and clinical detection feasibility of single or combined use of MIL with multi-tumor markers on different tumors.

Updated mechanisms underlying sickle cell disease-associated pain.

Sickle cell disease (SCD) is one of the most common severe genetic diseases around the world. A majority of SCD patients experience intense pain, leading to hospitalization, and poor quality of life. Opioids form the bedrock of pain management, but their long-term use is associated with severe side effects including hyperalgesia, tolerance and addiction.

Effects of microRNA-208a on inflammation and oxidative stress in ketamine-induced cardiotoxicity through Notch/NF-κB signal pathways by CHD9.

MicroRNA can regulate gene expression, and participate in multiple vital activities, such as inflammation, oxidative stress epigenetic modification, cell proliferation, and apoptosis. It plays an important role in the genesis and development of cardiovascular disease. To assess the role of microRNA-208a in ketamine-induced cardiotoxicity.

Safflower Yellow B Protects Brain against Cerebral Ischemia Reperfusion Injury through AMPK/NF-kB Pathway.

Inflammation had showed its important role in the pathogenesis of cerebral ischemia and secondary damage. Safflower yellow B (SYB) had neuroprotective effects against oxidative stress-induced brain injuries, but the mechanisms were still largely unknown to us. In this study, we tried to investigate the anti-inflammation effects of SYB and the possible roles of AMPK/NF-B signaling pathway on these protective effects.

DNMT3a-triggered downregulation of K 1.1 gene in primary sensory neurons contributes to paclitaxel-induced neuropathic pain.

Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K 1.1 controls neuronal excitability by setting the resting membrane potential.

Riluzole induces LTD of spinal nociceptive signaling via postsynaptic GluR2 receptors.

Purpose: Riluzole - a major therapeutic medicine for patients with amyotrophic lateral sclerosis - reportedly has anti-nociceptive and anti-allodynic efficacies in neuropathic pain models. However, little is known about its effect on neurotransmission in the spinal superficial dorsal horn (SDH). The present study aims to investigate the effects of riluzole on the synaptic transmission of SDH nociceptive pathways in both physiological and pathological conditions.

Ophthalmic branch radiofrequency thermocoagulation for atypical trigeminal neuralgia:a case report.

Background: Trigeminal neuralgia is an intense neuralgia involving facial areas supplied by trigeminal nerve. The pain is characterized by sudden onset, short persistence, sharp or lancinating. Trigeminal neuralgia commonly affects frontal areas, infraorbital or paranasal areas, mandibular areas and teeth.