Desipramine induces anti-inflammatory dorsal root ganglion transcriptional signatures in the murine spared nerve injury model

TL;DR

Desipramine, an antidepressant, reduces inflammation in nerve injury models by altering gene activity in sensory nerve cells.

Contribution

Desipramine induces unique anti-inflammatory gene signatures in dorsal root ganglia after nerve injury.

Findings

Desipramine counteracts injury-related gene changes in dorsal root ganglia.

Desipramine promotes anti-inflammatory gene expression in nerve-injured animals.

Desipramine's effects differ across pain-related brain regions after long-term injury.

Abstract

•Desipramine counteracts spared nerve injury-associated transcriptional signatures in the dorsal root ganglia.•Desipramine induces an anti-inflammatory transcriptional signature in the dorsal root ganglia of nerve injured animals.•Transcriptional effects of desipramine vary across pain processing regions after prolonged nerve injury.

Desipramine counteracts spared nerve injury-associated transcriptional signatures in the dorsal root ganglia.

Desipramine induces an anti-inflammatory transcriptional signature in the dorsal root ganglia of nerve injured animals.

Transcriptional effects of desipramine vary across pain processing regions after prolonged nerve injury.

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 L3-6 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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