Common transcriptional signatures of neuropathic pain.
Pokhilko A., Nash A., Cader MZ.
The dorsal root ganglia is a key structure in nociception and chronic pain disorders. Several gene expression studies of dorsal root ganglia in pre-clinical pain models have been performed, but it is unclear if consistent gene changes are identifiable. We, therefore, compared several recent RNA-Seq datasets on the whole dorsal root ganglia in rodent models of nerve injury. Contrary to previous findings, we show hundreds of common differentially expressed genes and high positive correlation between studies, despite model and species differences. We also find, in contrast to prior studies, that 60% of the common rodent gene response after injury is likely to occur in nociceptors of the dorsal root ganglia. Substantial expression changes are observed at a one-week time-point, with smaller changes in the same genes at a later three to four-week time-point. However, a subset of genes shows a similar magnitude of changes at both early and late time-points, suggesting their potential involvement in the maintenance of chronic pain. These genes are centred around suppression of endogenous opioid signalling. Reversal of this suppression could allow endogenous and exogenous opioids to exert their analgesic functions and may be an important strategy for treating chronic pain disorders. Currently used drugs, such as amitriptyline and duloxetine, do not appear to appropriately modulate many of the critical pain genes and indeed may transcriptionally suppress endogenous opioid signalling further.