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

• Published in: Cell reports (Cambridge) Vol. 43; no. 8; p. 114614
• Main Authors: Bangash, M. Ali, Cubuk, Cankut, Iseppon, Federico, Haroun, Rayan, Garcia, Chloe, Luiz, Ana P., Arcangeletti, Manuel, Gossage, Samuel J., Santana-Varela, Sonia, Cox, James J., Lewis, Myles J., Wood, John N., Zhao, Jing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.08.2024; Elsevier
• Subjects: Animals; CP: Neuroscience; Female; Ganglia, Spinal - metabolism; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Male; Mice; Mice, Inbred C57BL; NAV1.7 Voltage-Gated Sodium Channel - genetics; NAV1.7 Voltage-Gated Sodium Channel - metabolism; Pain - metabolism; Polyribosomes - metabolism; Protein Biosynthesis; Sensory Receptor Cells - metabolism; CP: Neuroscience
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114614

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 (plus nerve growth factor), and pain-free conditions (Nav1.7-null mice). The majority (98%) of translated transcripts are shared between male and female mice in both the somata and terminals. Some transcripts are highly 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 behavior. Terminal-enriched transcripts included those encoding synaptic proteins (e.g., synaptotagmin), non-coding RNAs, transcription factors (e.g., Znf431), proteins associated with transsynaptic trafficking (HoxC9), GABA-generating enzymes (Gad1 and Gad2), and neuropeptides (Penk). Thus, central terminal translation may well be a significant regulatory locus for peripheral input from sensory neurons. [Display omitted] •TRAP was used to find polysome-associated mRNA in mouse DRG somata and central terminals•Pain-free, normal, and pain states produce different mRNA expression profiles•Somata and terminal translatomes show significant differences•Translational knockdown of some pain-induced genes results in pain relief Bangash et al. adapted translating ribosome affinity purification technology to examine polysome-associated transcripts in both somata and central terminals of dorsal root ganglion neurons and identify potential candidates involved in pain pathways. They find that translational knockdown of Gnas, Nos1ap, Necab2, Ube2f, and Thoc7 significantly alter pain thresholds in mice.