Diabetic
neuropathy, or nerve damage, is one of the most painful complications faced
by people with diabetes.  Over time, high
blood sugar associated with diabetes may lead to nerve damage.  In the legs and feet, this nerve damage
frequently results in numbness or lack of sensation, but it can also lead to
intense pain.  Until now, researchers
have not understood exactly why nerve disease leads to this pain, which is difficult
to treat and can negatively affect a person’s quality of life.

Now, a new study has discovered one cause of pain for people
with nerve damage from diabetes.  The results
of the study, funded in part by JDRF through a center
grant and conducted by an international collaboration of researchers
including Dr.
Michael Brownlee and the late Dr. Angelika Bierhaus,
were published in the journal Nature Medicine.  In the study, conducted in mice, the researchers
found that a molecule called methylglyoxal (MG), which is produced
excessively from glucose in people with diabetes, contributes to the pain.  In the mice in the study, the excess MG bound
to a protein called Nav 1.8, which is found in a specific type of nerve cell
responsible for the sensation of pain. 
When this bond occurs, the nerve becomes locked in the “on” position,
resulting in the feeling of pain that accompanies nerve damage in people with
diabetes.

Since researchers now better understand what causes the
severe pain associated with diabetic neuropathy, they can use that knowledge to
develop new treatments.  According to Dr.
Brownlee, the study “opens the way for new diabetic neuropathy treatments
targeting methylglyoxal accumulation.” 
One possible approach is to regulate an enzyme called glyoxalase 1,
which may be able to prevent or remove the modifications caused by MG and
therefore eliminate the pain.  According
to Dr. Helen Nickerson, JDRF’s senior scientific program manager for treatment
therapies, “better understanding the role of methyglyoxal could lead to
potential therapy for more than one complication of diabetes.”

This study highlights one of the approaches JDRF is taking
in its research strategy
to prevent complications.  This
approach is to identify pathways triggered by high glucose levels over time
that eventually lead to complications, and attempt to intervene in the process
as early as possible to prevent them.