People who say they are more sensitive to pain than others could be right.

WORKSTREAMS NEWS December 2006

People who say they are more sensitive to pain than others could be right.
Researchers in the US said they had found a gene that appears to affect
how people feel discomfort. Tests in rats showed that blocking increased
activity of the gene after nerve injury or inflammation could prevent the
development of chronic pain, a finding that points to possible ways to
develop new pain drugs.

Studies in volunteers showed that about a quarter of them had the genetic
variant that protects them from pain somewhat, and three per cent carried
two mutated copies that made them exceptionally insensitive to pain, the
researchers reported in the journal Nature Medicine.

“This is a completely new pathway that contributes to the development of
pain,” said Dr Clifford Woolf of Massachusetts General Hospital and Harvard
Medical School in Boston, who led the research. “The study shows that we
inherit the extent to which we feel pain, both under normal conditions and
after damage to the nervous system.”

The affected gene is called GCH1, which codes for an enzyme called
GTP cyclohydrolase. This enzyme is needed to produce a chemical
called tetrahydrobiopterin or BH4. “Our results tell us that BH4 is a
key pain-producing molecule - when it goes up, patients experience
pain, and if it is not elevated, they will have less pain,” Dr Woolf said
in a statement. “The data also suggest that individuals who say they
feel less pain are not just stoics but genuinely have inherited a molecular
machinery that reduces their perception of pain.

“This difference results not from personality or culture, but real
differences in the biology of the sensory nervous system.”
Dr Woolf and researchers in Germany and at the US National Institutes
of Health said that rats with pain caused by nerve damage had higher
levels of GCH1 gene activity and of BH4.

When they injected a drug that interferes with GTP cyclohydrolase,
the enzyme controlled by the gene, the rats seemed less sensitive to
the pain. Injecting BH4 greatly increased pain sensitivity, they found.
The researchers tested 400 healthy people and found that volunteers
with two copies of the protective gene variant were less sensitive to
pain in tests.

People with two copies of the protective version of GCH1 had the
lowest risk of developing chronic pain, while those with just one copy
had an intermediate risk and those with no copies of the variant had
the highest risk.

The drug used in the study, DAHP, is not very strong and is unlikely
to be useful as a human medication, said D Woolf, who owns stock in
a company called Solace Pharmaceuticals, which has licensed the
findings for potential drug development.