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Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that, in mice, changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell type-specific profiling revealed that spinal inhibitory and excitatory neurons exhibited substantial changes in translation after peripheral nerve injury. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV+) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV+ neurons decreased their intrinsic excitability and spiking activity. Conversely, reducing translation in spinal PV+ neurons prevented the nerve injury-induced decrease in excitability but did not alleviate mechanical hypersensitivity. Together, these findings advance our understanding of translational control mechanisms in the spinal cord during neuropathic pain and highlight their cell type- and phase-specific contributions to gene expression and pain hypersensitivity.
Pubmed ID: 41960785
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Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsSoftware Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.
View all literature mentionsThe Canadian Institutes of Health Research (CIHR) is the Government of Canada''s agency responsible for funding health research in Canada. CIHR was created in 2000 under the authority of the CIHR Act and reports to Parliament through the Minister of Health. CIHR''s budget for 2008-09 is $928.6 million, of which $132 million is allocated to administering the Networks of Centres of Excellence and Canada Research Chair programs. CIHR was created to transform health research in Canada by: * funding more research on targeted priority areas; * building research capacity in under-developed areas such as population health and health services research; * training the next generation of health researchers; and * focusing on knowledge translation, so that the results of research are transformed into policies, practices, procedures, products and services. CIHR consists of 13 virtual institutes, a structure that is unique in the world. These innovative institutes bring together all partners in the research process - the people who fund research, those who carry it out and those who use its results - to share ideas and focus on what Canadians need: good health and the means to prevent disease and fight it when it happens. Each institute supports a broad spectrum of research in its topic areas and, in consultation with its stakeholders, sets priorities for research in those areas.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsNational institute whose mission is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world. To accomplish this goal the NINDS supports and conducts basic, translational, and clinical research on the normal and diseased nervous system. The Institute also fosters the training of investigators in the basic and clinical neurosciences, and seeks better understanding, diagnosis, treatment, and prevention of neurological disorders. NINDS: * Conducts, fosters, coordinates, and guides research on the causes, prevention, diagnosis, and treatment of neurological disorders and stroke, and supports basic research in related scientific areas. * Provides grants-in-aid to public and private institutions and individuals in fields related to its areas of interest, including research project, program project, and research center grants. * Operates a program of contracts for the funding of research and research support efforts in selected areas of institute need. * Provides individual and institutional fellowships to increase scientific expertise in neurological fields. * Conducts a diversified program of intramural and collaborative research in its own laboratories, branches, and clinics. * Collects and disseminates research information related to neurological disorders.
View all literature mentionsSoftware application for assembling of RNA-Seq alignments into potential transcripts. It enables improved reconstruction of a transcriptome from RNA-seq reads. This transcript assembling and quantification program is implemented in C++ .
View all literature mentionsProvides digital infrastructure, data analytics and decision support tools to help in diagnosis, treatment and monitoring of patients.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets IgG
View all literature mentionsThis monoclonal secondary targets IgG
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