New research has uncovered a target for chronic and pathologic pain, which could lead to better drugs for those affected by pain in the future.
Chronic pain is “the most common cause of long-term disability,” according to the National Institutes of Health (NIH).
In fact, a recent analysis from the NIH estimates that more than 25 million people in the United States (or over 11 percent of the country’s adult population) live with chronic pain. This means that they have experienced pain every day for the past 3 months.
While in some cases chronic pain may have been initially triggered by an incident such as an injury or an infection, most of the time, the cause of chronic pain is unknown.
Because its causes remain largely unknown, chronic pain cannot yet be cured. However, drugs usually help, and researchers are hard at work trying to come up with more effective treatments.
Now, a new study – published in the journal PLOS Biology – has identified a potential novel therapeutic target for chronic pain, which could help researchers to develop an alternative medication to treat pain in the near future.
The team was led by Dr. Matthew Dalva, of the Department of Neuroscience at Thomas Jefferson University in Philadelphia, PA. He and his team have investigated a process called phosphorylation and its impact on how chronic pain occurs and what sensations it triggers.
Phosphorylation is a term that describes a common biological process whereby a protein changes in response to external stimuli.
Previous research has identified a pain receptor called N-methyl-D-aspartate (NMDA) and the fact that it plays a key role in pathologic pain.
However, this receptor is also important in memory and learning, so drugs that would target this receptor would also affect these functions.
But in the new study, Dr. Dalva and colleagues identified a second receptor that also plays a crucial role in pain. In their study, the scientists examined neurons in particular.
Specifically, by conducting a series of laboratory tests in cell cultures and in vivo, the team were able to see that, in response to injury-induced pain, the protein ephrin B modifies outside of the brain cell. This phosphorylation outside of the cell allows the ephrin B receptor to attach to the NMDA receptor, moving it into the synapses.
This process alters the function of the NMDA receptor, which leads to higher sensitivity to pain.
As the authors explain, pathologic pain differs from pain caused by an injury or inflammation because it is a result of cellular dysfunction.
Because pain occurs at the cellular level, it does not go away even after the initial cause has gone – as is the case with chronic pain or the common migraine.
For a cell to function properly, proteins must be in the right location. But what the new study shows is that in the case of chronic pain, the so-called process of phosphorylation “moves” the proteins away from the neuron, thus triggering cell dysfunction and pathologic pain.
Importantly, using a mouse model, the scientists were also able to test some chemicals that managed to block the unwanted synergy between the ephrin B receptor and the NMDA receptor.
Interrupting this communication between the two receptors stopped the pain. And conversely, bringing the two receptors together led to an excessive sensitivity to pain.
The senior author of the study comments on the significance of the findings, saying, “Because the protein modification that initiates nerve sensitivity to pain occurs outside of the cell, it offers us an easier target for drug development. This is a promising advance in the field of pain management.”
“Although we have yet to discover the exact mechanism that causes this modification […] this finding offers both a target for developing new treatments and a strong new tool for studying synapses in general.”
Dr. Matthew Dalva