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Hippocampal CA3 Nex+ neuronal TNFR2 alleviates chronic neuropathic pain by sex-dependently engaging opioid and endocannabinoid pathways

GSE333494 Mus musculus (mouse) RNA-seq (gene expression) 26 samples Submitted 2026/06/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 26 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
26 samples: 6 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Chronic neuropathic pain develops due to persistant neuroinflammation and maladaptive synaptic plasticity in the central nervous system following nerve injury. While TNFR2 signaling has been extensively studied in pain resolution, its expression on specific neuronal populations and the molecular pathways involved in spontaneous pain recovery remain unknown.
Read the full summary ↓
In this, study, we investigated the role of TNFR2 within hippocampal Nex/Neurod6+ pyramidal neurons in promoting recovery from chronic constriction injury (CCI). To achieve neuron-specific deletion of TNFR2, we generated tamoxifen-inducible conditional knockout mice (NexCreERT2:TNFR2F/F). We demonstrate that TNFR2 deletion from Nex/Neurod6+ neurons prevents spontaneous pain recovery in both sexes. Exogenous administration of a TNFR2 agonist significantly improved mechanial withdrawal thresholds in both sexes of wld-type mice but did not alleviate pain in NexCreERT2:TNFR2F/F, indicating that Nex-TNFR2 expression is required for TNFR2-mediated analgesia. Bulk RNA sequencing of hippocampal (Hc) tissue collected six weeks after CCI revealed that TNFR2 activation upregulates genes Pomc and oleoyl-ACP-hydrolase (Olah). Immunostaining also showed that TNFR2 agonism restored cornu ammonis 3 (CA3) region POMC and β-Endorphin protein levels that were suppresed after CCI. A behavioral experiment demonstrated that systemic blockade of the u-opioid receptor with naltrexone prevented TNFR2-mediated pain recovery in males but only partially in females. In contrast, inhibition of cannabinoid 1 receptor (CB1R) signaling abolished TNFR2-driven analgesia in both sexes. Together, these data reveal that Hc TNFR2 signaling in Nex+ neurons is critical for CNP recovery and TNFR2 acivation promotes analgesia by engaging endogenous u-opioid and endocannabinoid pathways in a sex-dependent manner
This dataset
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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE333494_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1471192 and SRA study SRP704196. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly with about 4 replicates each
CCI/R2A_FF ×5 CCI/R2A_CFF ×5 Naïve_FF ×4 Naïve_CFF ×4 CCI/P_FF ×4 CCI/P_CFF ×4

Supports a between-group comparison across 26 samples.

How we read this: 6 replicated groups read from 26 sample titles; they account for 26 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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