Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury.

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA­seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)]were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)­mRNA regulatory network and miRNA­target gene­pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co­expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA­mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were revealed according to the miRNA­target gene­pathway regulatory network to be related to NP. Four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.

Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury.

Our study aimed to explore the molecular mechanisms and novel target genes of neuropathic pain via bioinformatics analysis. Gene expression profiling of GSE30691 which was consisted of sciatic nerve lesion and sham control samples at 3 days, 7 days, 21 days, and 40 days (D3, D7, D21, and D40) after injury were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified for all the four time points. Overlapped DEGs for all the four time points were used for functional and weighted co-expression modular analysis. Afterwards, protein-protein interaction (PPI) network was analyzed by MCODE (Molecular Complex Detection) and BiNGO. Pathway network was constructed according to the enriched pathways of PPI network and relevant pathways selected from the Comparative Toxicogenomics Database. There were 355 overlapped DEGs for all the four time points. Two co-expression modules had significant positive correlations with disease. The top ten hub DEGs in the PPI network were Fos, Tp53, Csk, Map2k2, Stat3, Ccl2, Pxn, Tgfb1, Notch1, and Prkacb. Fos, Dusp1, Tp53, Tgfb1, and Map2k2 participated in MAPK signaling pathway, while Csk participated in chemokine signaling pathway. The expressions of Fos, Tp53, Csk, and Map2k2 were significantly increased at D3. Tp53, Csk, and Map2k2 continued overexpressing until at D7, and an elevated tendency in Csk expression could be observed until at D21. The expression of Fos reached up to the highest at D40. Fos, Tp53, Csk, and Map2k2 might be the potential biomarkers related to neuropathic pain.

A resting-state study of volumetric and functional connectivity of the habenular nucleus in treatment-resistant depression patients.

OBJECTIVE: To investigate the volumetric and functional connectivity of the habenular nucleus in treatment-resistant depression (TRD) patients using the resting-state functional magnetic resonance imaging (rs-fMRI) approach. METHODS: A total of 15 TRD patients, who visited the Mental Health Institute of the First Hospital Affiliated with Jilin University between August 2014 and March 2015, along with 15 normal subjects, were enrolled into this study for structural and functional imaging. Functional connectivity analysis was performed using bilateral habenular nuclei as the region of interest in contrast to whole-brain voxels. RESULTS: No significant difference of absolute volume was found in bilateral habenular nuclei between TRD patients and healthy controls, or after controlling for individual total intracranial volume. However, functional connectivity analysis showed increased connectivity between the right habenular nucleus with the medial superior frontal gyrus, anterior cingulate cortex and medial orbitofrontal gyrus, and decreased connectivity with the corpus callosum in the TRD group. For the left habenular nucleus seed, the brain region with increased functional connectivity in the inferior temporal gyrus and decreased functional connectivity in the insular was found in the TRD patients. CONCLUSION: Abnormal functional connectivity was present between the habenular nucleus and the default mode network in TRD patients. Dysfunction in habenular nucleus-related circuitry for processing negative emotion might form the pathological basis for TRD. Significant asymmetric functional connectivity was also found between bilateral habenular nuclei in TRD patients. Such asymmetry suggests potentially divergent strategy for intervention on bilateral habenular nucleus regions in the future management of depression.