Harry Epstein, the then Chair of the Department of Neuroscience and Cell Biology at UTMB, once told me that as scientists working on pain, we are unknowingly working on neural plasticity. This is clearly the theme of the article by Zhao and colleaguesCitation1 in this issue of the Journal. Having queried the Gene Expression Omnibus (GEO) database they concluded that nerve injury leads to critical changes in the expression of genes in dorsal root ganglia (DRG). Why the DRG? Because this is where all the cell bodies of peripheral neurons are gathered, surrounded by satellite glial cells that outnumber the neuronal counter part by 1 to 10.Citation2 Once nerves have been transected the DRG orchestrates a desperate attempt at restoring previous connections with the peripheral organs, skin, muscles and joints. Some of the usual suspect molecules such as Jun and P53 are critically involved in this regenerative and often painful process. New findings also bring our attention to the concept of “hub genes”, which is not yet part of the pain scientists “lingo” despite that the expression dates back to 2005 or likely earlier. Hub genes belong to the gene regulatory network and, as the name suggests, interact with many other genes that are at nodal points in the network of events. These genes are essential to our understanding of regeneration, tumor genesis and probably everything that can go wrong in biology. The role of the 13 hub genes reported by Zhao in the DRG, however, still needs to be clarified. Rightfully the authors argue that these should be the key focus of our efforts, a conclusion echoed in previous studies.Citation3 And while one might be tempted to call them pain genes, I would suggest that in its acute phase nociceptive sensation is just one of the many adverse events linked to the regenerative process. In the future, we will need much better algorithms and processing power to figure out the complexity of nature's regenerative processes. I hope that wherever you are Henry, you are pleased to see that a pain scientist acknowledges what we are really focused on.
DECLARATION OF INTEREST
The author reports no conflicts of interest. The author alone is responsible for the content and writing of this commentary.
ACKNOWLEDGMENTS
I would like to express my appreciation to Eve Jasmin for reviewing the text.
REFERENCES
- Zhao H, Duan LJ, Sun QL, et al. Identification of key pathways and genes in L4 dorsal root ganglion (DRG) after sciatic nerve injury via microarray analysis. J Invest Surg. (in press).
- Jasmin L, Vit JP, Bhargava A, Ohara PT. Can satellite glial cells be therapeutic targets for pain control? Neuron Glia Biol. 2010;6(1):63–71. doi:10.1017/S1740925X10000098. PMID:20566001.
- Li S, Xue C, Yuan Y, et al. The transcriptional landscape of dorsal root ganglia after sciatic nerve transection. Sci Rep. 2015;5:16888. doi:10.1038/srep16888. PMID:26576491.