TRPV1 DRG: Identification of a sacral, visceral sensory transcriptome in embryonic and adult mice

Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially lead to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively somatic sensory neurons. This was performed in male and female mice (adult and E18.5). By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal level. We identified many novel genes not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways. Donor matched comparison of dorsal root ganglia from lumbar and sacral spine regions in adult Trpv1tm2Bbm mice内脏感觉神经元（Visceral sensory neurons）可编码来自健康器官的特异性感觉信号，并介导对常规镇痛剂耐受的疼痛状态。转录组分析正革新我们对感觉神经元亚型的认知，但既往研究多聚焦于躯体感觉神经元，或以神经元总群体为研究对象——其中内脏感觉神经元占比极低。本研究旨在明确骶部内脏感觉神经元特异性表达的转录本，以期解析这类神经元的独特生物学特性，并有望为盆腔内脏痛发现全新镇痛靶点。我们的研究策略为：对比包含躯体神经元与骶部内脏神经元的骶部背根神经节（dorsal root ganglia, DRG），与仅含躯体感觉神经元的邻近腰部背根神经节之间的差异表达基因。实验对象涵盖雌雄成年小鼠及胚胎期18.5天（E18.5）小鼠。通过开发限定分析对象为伤害性感受TRPV1神经元的方法，我们在脊髓节段间检测到了更多差异表达基因。本研究鉴定出诸多此前未被关联于盆腔内脏感觉或伤害性感受的全新基因。在感觉神经节的整体转录组中，性别差异较为有限，但在骶部节段，尤其是TRPV1阳性伤害性感受神经元中，性别差异更为显著。上述数据将助力开发调控成熟与发育中感觉神经元及伤害性感受通路的新型工具。本研究针对成年Trpv1tm2Bbm小鼠的腰部与骶部脊柱区域背根神经节开展供体匹配对照分析。