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Despite the fact that chronic pain is one of the most prevalent health problems, the widespread treatment for alleviating it consists of non-steroidal anti-inflammatory drugs (NSAIDS), opioid analgesic drugs, anticonvulsants and antidepressants. These drugs have limited efficacy since the pain is relieved in only half the individuals receiving these drugs, that too only temporarily.
This research aimed to identify the cellular mechanisms that regulate chronic pain in an effort to improve the currently practiced treatments. The study was carried out by scientists at Drexel University College of Medicine and was led by Melissa Manners, PhD, supervised by Seena Ajit, PhD, assistant professor at College of Medicine. The study was subsequently published in Epigenetics & Chromatin.
Genetic Regulators of Chronic Pain Unearthed
The researchers discovered that the DNA-binding protein methyl-CpG-binding protein 2 (MeCP2) controls the expression of various genes involved in the regulation of chronic pain. By binding to the DNA, this protein alters the expression of genes, causing considerable changes in the genetic pathways of chronic pain.
It was discovered that this is the same protein whose mutation results in Rett syndrome, an autistic spectrum disorder that affects girls more than boys. The patients of Rett Syndrome have been found to have a higher threshold for pain which led the scientists to theorize that MeCP2 is involved in the regulation of pain perception.
A study of the dorsal root ganglia of the spinal nerves established that injuries to the nerves can alter the way in which MeCP2 binds to the DNA which, in turn, causes changes in the genes controlling pain. Owing to the extremely small size of the dorsal root ganglia, this study was particularly difficult to perform. The level of MeCP2 was invariably found to be elevated following the nerve injuries.
Genetic Basis of Chronic Pain
The next big step was to pin down the specific genes that are regulated by methyl-CpG-binding protein 2 (MeCP2). For this, the scientists conducted a large scale study to recognize the pattern of binding of DNA in the dorsal root ganglia of the spinal nerves. The scientists strived to identify the sequence of DNA in the genome of mice, especially those that are bound by MeCP2 and to study the changes in these sequences after nerve injuries.
It was determined that after injury to the nerves, the pattern of attachment of MeCP2 moved towards the parts of DNA that code for proteins and RNA. These findings led the scientists to the conclusion that the binding of MeCP2 to the DNA is not limited to a few genes only and wide areas of the DNA are bound due to which a large number of genes are involved in the regulation of chronic pain.
This study has proved to be a big step forward towards identifying the exact molecular and genetic mechanisms of chronic pain. Since a broad number of genes are involved in the expression of pain, it is very difficult to come up with a single drug that can affect all these genes simultaneously. However, further studies can help identify the target areas of MeCP2 which can lead to the formulation of better treatment plans.