Nearly half of all diabetics suffer from
neuropathic pain, an intractable, agonizing and still mysterious companion of
the disease. Now Yale researchers have identified an unexpected source of the
pain and a potential target to alleviate it.
A team
of researchers from Yale and the West Haven Veterans Affairs Medical Center
describes in the May 15 issue of the Journal of
Neurosciencehow changes in the structure of dendritic spines –
microscopic projections on the receiving branches of nerve cells – are
associated with pain in
laboratory rats with diabetes.
"How
diabetes leads to neuropathic
pain is still a mystery," said Andrew Tan, an associate research
scientist in neurology at the Yale School of Medicine and lead author of the
study. "An interesting line of study is based on the idea that neuropathic
pain is due to faulty 'rewiring' of pain circuitry."
With a
growing number of diabetics, the condition represents a huge unmet medical
need. Once neuropathic pain is established, it is a lifelong condition.
"Here
we reveal that these dendritic spines, first studied in memory circuit
processing, also contribute to the sensation of pain in diabetes," Tan
said. A single neuron may contain hundreds to thousands of dendritic spines.
The
Yale team led by Tan and senior author Stephen G. Waxman, Bridget Marie
Flaherty Professor of Neurology, professor of neurobiology and pharmacology,
found abnormal dendritic spines were associated with the onset and maintenance
of pain. They also found that a drug that interferes with formation of these
spines reduced pain in lab animals, suggesting that targeting abnormal spines
could be a therapeutic strategy.
Tan
said that these dendritic spines in nerve cells seem to store memory of pain,
just as they are crucial in memory and learning in the human brain.
"We
have identified a single, key molecule that controls structural changes in
these spines and
hopefully we can develop therapeutic approaches that target that molecule and
reduce diabetic pain," Waxman said.
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