Journal
PAIN
Volume 162, Issue 1, Pages 203-218Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000002007
Keywords
Dorsal horn; Spinal cord; Gene expression; RNA-seq; sNuc-Seq; Single cell; Single nucleus; Transcriptomics; INTACT; Pain; Neonatal; Neuronal
Categories
Funding
- National Institutes of Health [NS100469]
Ask authors/readers for more resources
Neonatal tissue damage may have long-term effects on nociceptive processing in the central nervous system, with pDyn neurons in the spinal dorsal horn playing a crucial role. Research identified gene expression changes in adult pDyn neurons following neonatal tissue injury, with genes related to cellular stress response being highlighted, suggesting that posttranscriptional regulation may play a key role in the activation of nociceptive circuits by early-life injury.
Neonatal tissue damage can have long-lasting effects on nociceptive processing in the central nervous system, which may reflect persistent injury-evoked alterations to the normal balance between synaptic inhibition and excitation in the spinal dorsal horn. Spinal dynorphin-lineage (pDyn) neurons are part of an inhibitory circuit which limits the flow of nociceptive input to the brain and is disrupted by neonatal tissue damage. To identify the potential molecular underpinnings of this disruption, an unbiased single-nucleus RNAseq analysis of adult mouse spinal pDyn cells characterized this population in depth and then identified changes in gene expression evoked by neonatal hindpaw incision. The analysis revealed 11 transcriptionally distinct subpopulations (ie, clusters) of dynorphin-lineage cells, including both inhibitory and excitatory neurons. Investigation of injury-evoked differential gene expression identified 15 genes that were significantly upregulated or downregulated in adult pDyn neurons from neonatally incised mice compared with naive littermate controls, with both cluster-specific and pan-neuronal transcriptional changes observed. Several of the identified genes, such as Oxr1 and Fth1 (encoding ferritin), were related to the cellular stress response. However, the relatively low number of injury-evoked differentially expressed genes also suggests that posttranscriptional regulation within pDyn neurons may play a key role in the priming of developing nociceptive circuits by early-life injury. Overall, the findings reveal novel insights into the molecular heterogeneity of a key population of dorsal horn interneurons that has previously been implicated in the suppression of mechanical pain and itch.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available