Could Gabapentin Make my Pain Go Away?

Study suggests that gabapentin could act on certain proteins that are deregulated in endometriosis and be effective in reducing endometriosis-associated pain.

Key Points

Highlights:

Researchers identified a set of genes that are deregulated in human endometriosis implants and mutant mice that have an endometrial phenotype. Some of these genes encode for proteins that are involved in pain perception.

Importance:

Targeting these proteins with medication such as gabapentin could effectively reduce endometriosis-associated pain.

What's done here:

Researchers analyzed the genes that are deregulated in endometriosis and in the uterus of mutant mice that have an endometrial phenotype. 

Key results:

• There was a strong reduction in the expression of the transcription factor DLX5 in endometriosis implants. 
• There were 30 genes that were deregulated both in human endometriosis implants and in the uterus of mice lacking DLX5 and another similar transcription factor DLX6. 
• Three components of the α2δ family of voltage-dependent calcium channel complex, which is known to be involved in pain perception were overexpressed both in endometriosis implants and the uterus of the mutant mice. 

Limitations:

The findings are based on experiments conducted in the laboratory and in animal models. Human clinical trials are needed to confirm the potential benefits of gabapentin in reducing chronic pelvic pain. 

Lay Summary

Gabapentin could effectively reduce endometriosis-associated pain, according to a new study published in the Journal of Pain Research.

The study that was conducted in mice and endometriotic tissues from patients suggests that certain proteins present on the surface of cells and that are involved in the perception of pain could be playing an important role in endometriosis symptoms such as chronic pelvic pain. Therefore, targeting these proteins with medication could be effective in treating endometriosis-associated pain.

Previous research has shown that two transcription factors or proteins that regulate the production of other proteins, called DLX5 and DLX6 are under-produced in endometriotic lesions compared to normal endometriotic tissues. Moreover, inactivating these two proteins in the uterus of mice models led to symptoms similar to endometriosis in the animals. These findings suggest that biological processes involving DLX5 and DLX6 might also be involved in endometriosis.

In order to further understand the possible role of DLX5, DLX6, and other proteins that might be involved in endometriosis-associated pain, researchers led by Dr. Giovanni Levi at the National Museum of Natural History, in Paris, France analysed genes that are deregulated in endometriosis and in mice that have been genetically modified not to produce any DLX5 or DLX 6 protein.  

Their results confirmed that there was a strong reduction in the production of DLX5 protein in endometriotic tissues implanted in animals. The researchers also identified 30 genes that were deregulated in a similar way both in human endometriosis implants and the uterus of their experimental mice. 

Three of these genes called CACNA2D3, CACNA2D1, and CACNA2D2 were strongly active, I.e. encoding for a protein, in both the endometriosis implants and the uterus of the mutant mice. The proteins that these genes encode for are part of the proteins present on cells surfaces and involved in the perception of pain.

These findings suggest that targeting these proteins with medication could be effective in reducing endometriosis-associated pain. Gabapentin is one such medicine, so the authors suggest that its use could be an option for women with endometriosis, but add that large-scale clinical trials are needed to test the potential benefit of gabapentin in treating chronic pelvic pain.

Gabapentin is a prescription medicine primarily used to treat epileptic seizures and pain associated with shingles. It is a strong painkiller first approved in the U.S. in 1993. It is classified as a controlled substance in some states in the U.S. because it has recently been linked to overdose deaths.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29692624