Chronic, often
intractable, pain is caused by neuropathic conditions such as traumatic
peripheral nerve injury (PNI) and
spinal cord injury (SCI). These conditions are associated with alterations in gene and
protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where
axotomy-induced changes important for neural regeneration may overshadow changes that drive
neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to
pain, but contusive SCI produces little peripheral
axotomy or peripheral nerve
inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight
pain-associated transcriptional alterations in sensory ganglia that do not depend on peripheral
axotomy or associated effects such as peripheral
Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of published whole-DRG
RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes (RAGs) and long noncoding RNAs (lncRNAs). Many transcriptomic changes after SCI also were found after corresponding
sham surgery, indicating they were caused by injury to surrounding tissue, including bone and muscle, rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between rat
neuropathic pain models and the only reported transcriptional analysis of human DRGs linked to
neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural injury and associated tissue damage. Although only a few genes in DRG cells exhibited similar changes in expression across all the painful conditions examined here, these genes may represent a core set whose transcription in various DRG cell types is sensitive to significant bodily injury, and which may play a fundamental role in promoting
neuropathic pain.