Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes

The relationship between transcription and protein expression is complex. We identified polysome-associated RNA transcripts in the somata and central terminals of mouse sensory neurons in control, painful (+NGF) and pain-free conditions (Nav1.7 null mice). The majority (98%) of translated transcripts are shared between male and female mice, as are transcripts in the somata and terminals. However, some transcripts are enriched in the somata or terminals. Changes in the translatome in painful and pain-free conditions include novel and known regulators of pain pathways. Antisense knockdown of selected somatic and terminal polysome-associated transcripts that correlate with pain states diminished pain behaviour. Terminal-enriched transcripts encoding synaptic proteins, non-coding RNAs, transcription factors, proteins associated with trans-synaptic trafficking, GABA-generating enzymes and neuropeptides suggest that central terminal translation is a significant regulatory locus for peripheral input from sensory neurons.<b>TRAP gene expression and samples annotation files</b><b>Raw gene counts</b><b>Normalized gene counts</b><b>Sample annotations</b>

转录过程与蛋白质表达之间的关联极为复杂。本研究在对照组、疼痛状态（添加神经生长因子（nerve growth factor，NGF）组）及无痛状态（Nav1.7基因敲除小鼠）中，成功鉴定了小鼠感觉神经元胞体与中枢终末内与多聚核糖体（polysome）结合的RNA转录本。绝大多数（98%）的翻译转录本在雌雄小鼠间共享，神经元胞体与神经终末中的转录本亦呈现相同的分布规律。但亦有部分转录本仅在胞体或神经终末中富集。疼痛与无痛状态下的翻译组（translatome）谱发生的变化，涵盖疼痛通路的新型及已知调控因子。对与疼痛状态相关的选定胞体及终末多聚核糖体结合转录本进行反义敲减（antisense knockdown），可显著缓解疼痛相关行为。编码突触蛋白、非编码RNA、转录因子、跨突触运输相关蛋白、γ-氨基丁酸（GABA）合成酶及神经肽的终末富集转录本表明，中枢终末的翻译过程是感觉神经元外周传入信号的关键调控位点。<b>TRAP基因表达及样本注释文件</b><b>原始基因计数数据</b><b>标准化基因计数数据</b><b>样本注释信息</b>