New research in mice suggests that targeting
a particular protein in the spinal cord could form the basis of a new pain
relief medication that could relieve chronic pain for thousands of people.
About one-fifth of adults in the United States are
living with chronic pain, which is a pain that lasts for longer than 3 months.
However, one specific type of chronic pain is of particular concern —
neuropathic pain.
Neuropathic pain results from nerve injury
and around 10% of the U.S. population
may be living with it. Due to rising life expectancy and contributory lifestyle
factors, estimates suggest that this figure will increase.
Neuropathic pain has a range of causes, including
physical injury to the nerves that send information between the spinal cord and
brain, viral infections, conditions such
as diabetes and multiple sclerosis,
medication side effects, and excessive alcohol consumption.
The cause does not alter the fact that
doctors find this type of pain challenging to treat. It can also significantly
impact a person's life, with symptoms ranging from burning and tingling to stabbing
and stinging.
Traditional pain relief medications are often
ineffective against neuropathic pain. As assistant professor Mette Richner from
Aarhus University, Denmark, puts it, people with neuropathic pain can try a
shopping basket of medications "without ever really getting any good
results."
But Richner and a team from the university
have identified a protein that could be an effective target for pain relieving
drugs. A decade's worth of research spurred the new study, published in the
journal Science
Advances.
How pain develops
Previous studies revealed that mice unable to produce sortilin,
which is a protein that occurs on the surface of nerve cells, seemed to feel no
pain after suffering nerve damage.
The researchers saw the same effect in
regular mice with nerve damage, but only when they blocked sortilin's path.
The team wanted to find out why. They already
knew that chronic pain occurred as a result of malfunctioning nerve cells. So
they used molecular techniques, including tissue and protein analyses, to
discover the link between sortilin and pain.
"And it's here, at the molecular level,
that we've now added a crucial piece to a larger puzzle," explains
Richner. That piece, in summary, is the role of sortilin in the pain
development process.
"Once nerve damage has occurred, and the
nerve cells go into overdrive, molecules are released, which start a domino
effect that ultimately triggers pain," she continues.
"The domino effect can be inhibited by a
particular molecule in the spinal cord called neurotensin, and our studies show
that the neurotensin is 'captured' by sortilin so that the brake is itself
inhibited."
From mice to humans
A drug that could stop sortilin in its tracks
could go some way to diminishing or stopping neuropathic pain altogether in the
human body.
The team note two limitations to the
research. One is that any further research into blocking sortilin will require
the help of the pharmaceutical industry. Secondly, the research took place in
mice, and the researchers cannot yet say whether they can apply the findings to
humans.
However, associate professor Christian B.
Vaegter is confident that blocking sortilin could have the same effect on humans.
"Our research is carried out in mice, but as
some of the fundamental mechanisms are quite similar in humans and mice, it
still gives an indication of what is happening in people [living with] chronic
pain."
Christian B. Vaegter
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