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Desipramine Induces Anti-inflammatory Dorsal Root Ganglion Transcriptional Signatures in the Murine Spared Nerve Injury Model

ABSTRACT: Desipramine Induces Anti-inflammatory Dorsal Root Ganglion Transcriptional Signatures in the Murine Spared Nerve Injury Model

PROVIDER: PRJNA1088405 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28352555_1.fastq.gz	Fastqsanger.gz
	SRR28352555_2.fastq.gz	Fastqsanger.gz
	SRR28352556_1.fastq.gz	Fastqsanger.gz
	SRR28352556_2.fastq.gz	Fastqsanger.gz
	SRR28352557_1.fastq.gz	Fastqsanger.gz

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Desipramine Induces Anti-inflammatory Dorsal Root Ganglion Transcriptional Signatures in the Murine Spared Nerve Injury Model

Project description:Monoamine-targeting antidepressants serve as frontline medications for chronic pain and associated comorbidities. While persistent anti-allodynic properties of antidepressants generally require weeks of treatment, several groups have demonstrated acute analgesic effects within hours of administration, suggesting a role in non-mesocorticolimbic pain processing regions such as the peripheral nervous system. To further explore this possibility, after four weeks of spared nerve injury or sham surgeries, we systemically administered desipramine or saline for an additional three weeks and performed whole transcriptome RNA sequencing on injured dorsal root ganglia. Along with alterations in molecular pathways associated with neuronal activity, we observed a robust immunomodulatory transcriptional signature in the desipramine treated group. Cell subtype deconvolution predicted that these changes were associated with A- and C-fibers. Of note, differentially expressed genes from the dorsal root ganglia of DMI-treated, injured mice were largely unique compared to those from the nucleus accumbens of the same animals. These observations suggest that, under peripheral nerve injury conditions, desipramine induces specific gene expression changes across various regions of the nociceptive circuitry.

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Project description:We report here a systematic approach to characterize the transcriptional responses of different cells types in the dorsal root ganglion (DRG) to peripheral nerve injury using single cell RNA sequencing (scRNAseq). We compare scRNAseq datasets of lumbar DRGs form naïve mice with corresponding datasets from mice subjected to spared nerve injury (SNI) 7 or 14 days prior to analysis. SNI surgery was performed in the left and right hindleg and development of mechanical allodynia was monitored by von Frey testing relative to control mice and the baseline level. Mice were perfused with PBS prior to extraction of L3 and L4 DRGs and DRGs were enzymatically and mechanically dissociated to single cell suspension before scRNAseq. Analysis of transcriptional changes in this nerve injury-paradigm reveals a differential response at 7 days versus 14 days post injury, suggesting dynamic gene modulation over time.

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