Major Differences in Transcriptional Alterations in Dorsal Root Ganglia Between Spinal Cord Injury and Peripheral Neuropathic Pain Models

Journal of Neurotrauma, 2023 · DOI: 10.1089/neu.2022.0238 · Published: May 1, 2023

Spinal Cord Injury Neurology Pain Management

Simple Explanation

Neuropathic pain, a chronic and often untreatable condition, can result from traumatic peripheral nerve injury (PNI) or spinal cord injury (SCI). These injuries lead to changes in gene and protein expression in sensory neurons, which are located in dorsal root ganglia (DRGs). This study compares the transcriptional signatures of DRGs in PNI and SCI models. The aim is to identify pain-associated transcriptional alterations in sensory ganglia that are independent of peripheral axotomy or associated effects like Wallerian degeneration. The research combines data from rat thoracic SCI experiments with meta-analysis of published RNA-seq datasets from rat PNI models. The findings reveal striking differences in transcriptional responses between PNI and SCI, especially in regeneration-associated genes (RAGs) and long non-coding RNAs (lncRNAs).

Study Duration

1 month

Participants

Male rats (200-300 g)

Evidence Level

Not specified

Key Findings

1
Significant differences exist in transcriptional responses to PNI and SCI, particularly in regeneration-associated genes (RAGs) and long non-coding RNAs (lncRNAs).
2
Many transcriptomic changes after SCI were also found after sham surgery, indicating that they were caused by injury to surrounding tissue, rather than the spinal cord itself.
3
Few transcriptomic similarities were found between rat neuropathic pain models and transcriptional analysis of human DRGs linked to neuropathic pain.

Research Summary

This study compares DRG transcriptional profiles in rat SCI and PNI models to identify pain-associated transcriptional alterations independent of peripheral axotomy. Data from rat thoracic SCI experiments were combined with meta-analysis of published RNA-seq datasets from rat PNI models. The study found striking differences in transcriptional responses between PNI and SCI, especially in regeneration-associated genes (RAGs) and long non-coding RNAs (lncRNAs). Many SCI-associated alterations in DRG gene expression were caused by surgical injury rather than cord injury. Few transcriptomic similarities were found between rat neuropathic pain models and human DRGs linked to neuropathic pain. However, genes exhibiting similar expression changes across all painful conditions examined may represent a core set important for promoting neuropathic pain.

Practical Implications

Targeted Therapies

Identifying core genes that consistently change expression across diverse, painful injury models may help development of targeted therapies.

Understanding Pain Mechanisms

The study underscores the complex transcriptional responses of DRGs to neural injury and associated tissue damage, providing insight into mechanisms driving persistent pain.

Refining SCI Models

The finding that surgical injury significantly contributes to DRG gene expression changes in SCI models suggests refining experimental designs to minimize confounding effects of tissue injury.

Study Limitations

1
The lack of temporal alignment between SCI-related and PNI-related transcriptomes may contribute to the differences in gene expression among the selected studies.
2
The most upregulated RAG found in rat neuropathic pain models, Sprr1a, is not differentially expressed in human DRGs.
3
The limited number of shared DEGs between rat and human DRGs.

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