Just like an antiviral drug might target viral machinery to prevent a pathogen from multiplying and causing infection, the Drexel researchers anticipated targeting the MeCP2-regulated genes to prevent nerve injury-induced chronic pain. MeCP2 controls the expression of these genes, meaning that the researchers don’t need to change the structure of the genes. They just need to change how they are expressed.
The science of gene expression, called epigenetics, is of growing interest in the research community. In the case of chronic pain, it seems like nerve injury causes changes in how MeCP2 binds genes and affects their expression, causing the sensation of constant, increased pain. Interestingly, a mutation in MeCP2 also causes an autism spectrum disorder called Rett syndrome. In addition to severe impairments in talking, moving, eating, and breathing, people with Rett syndrome have a higher tolerance for pain.
Was there a way to achieve a similar effect for people with chronic pain by altering the expression of certain MeCP2-regulated genes? Possibly. The next step was to pin down which genes are specifically regulated by MeCP2 that are also involved in causing chronic pain. Lead author of the Drexel study, Melissa Manners, PhD, focused on the dorsal root ganglia, a bundle of sensory neurons that transfer information between the peripheral nervous system and the spinal cord.
First, Manners and her team confirmed the role of MeCP2 in chronic pain: levels of the protein increased after nerve injury. Next, in a global study of the mouse genome in a chronic neuropathic pain state, the found that MeCP2 bound more genes coding for proteins and small non-protein coding regulatory RNA molecules when the mice were in chronic pain. Specifically, they discovered that MeCP2 binds chromatin, a complex that forms chromosomes from genetic material.
When MeCP2 binds chromatin, it influences the way certain genes are expressed, and scientists can now experiment with changing the expression of these genes. By understanding the pathway of pain centered on MeCP2, new effective and non-addictive targets for pain alleviation can be developed.
Manners’ study was recently published in Epigenetics & Chromatin.
Sources: Drexel University, Scitable by Nature Education, Yale Histology, International Rett Syndrome Foundation