18
Can pain be
'switched off'?
UK-News
"Pain 'dimmer switch' discovered by UK
scientists," reports BBC News. This headline comes from a DNA study that looked
at whether pain tolerance is linked to
"gene expression". Gene expression is the
influence that the "information" contained
in genes can have on a cellular level–in
most cases, it is the way specific proteins
are created.
The study included 50 identical twins who
were categorised as having either a low or
high pain threshold based on the results of
a heat probe test. The study found that
those with a low threshold had reduced
gene expression in nine regions of their
DNA.
Reduced gene expression – called "DNA
methylation" – is a natural process that
turns off various sections of DNA so that
cells can become specialised. It is also
seen in the ageing process. This study
found that in identical twins – who start
with the same DNA – nine regions of the
DNA had undergone more methylation in
those with a lower pain threshold. One of
the regions had already been identified as
being involved in pain response by previous research, but other regions had not.
The study has not looked at whether this
methylation process could be reversed or
if this would change the experience of
pain, so any potential new drug therapy is
still a long way off.
Where did the story come from? The study
was carried out by researchers from Pfizer
Research Laboratories and universities in
London, Oxford, Saudi Arabia, Denmark
and China, and was funded by the Wellcome Trust, the Royal Society Wolfson
Research Merit Award, and the European
Union (EU-FP7 projects).
It was published in the peer-reviewed
medical journal, Nature Communications.
The media generally reported the story accurately, although the "dimmer switch"
analogy, while eye-catching, is unhelpful.
It implies that less pain would be felt if the
gene expression was reduced, when in fact
it was the other way around–reduced gene
expression was responsible for a lower
pain threshold. It is also unclear whether
there are any mechanisms, such as new
painkillers, that could be used to "dim"
pain by affecting the rate of gene expression. What kind of research was this?
This was a case-control studyof identical
twins and unrelated people, which looked
at their pain tolerance and gene expression. It aimed to see if there was a link between lower pain threshold and different
levels of gene activity.
Identical twins have the same DNA, but
previous research has found that the individual genes may be more or less active
depending on biological, psychological
and environmental factors. The study of
these types of gene changes is known as
"epigenetics".
By looking at identical twins with a difference in pain threshold, the researchers
hoped to be able to pinpoint which genes
were less active.
This type of study cannot prove that certain gene activity is responsible for feeling
pain, but it can help researchers target new
areas for drug research.
What did the research involve? Researchers measured the pain tolerance of
identical twins. They selected 50 identical
twins who had the biggest difference in
pain threshold and took blood samples to
look at their DNA. They then repeated the
study in 50 unrelated people.
One hundred identical and non-identical
twins from the TwinsUK and Healthy
Ageing Twin study had quantitative sensory testing, which involved having a
probe placed on the forearm heated from
32°C up to a maximum 50°C.
The participant would say when the sensation of the temperature changed from
"painful" to "unbearable", and the temperature would be automatically recorded and
the experiment stopped.
A blood test was taken after the experiment to look at their DNA. The 50°C maximum was chosen so that the participants
did not get burned.
The researchers then chose the 25 pairs of
identical twins from this group who had
the largest difference in heat pain threshold and studied their DNA (age 46 to 76,
median age 62).
They performed the experiment again two
to three years later in 50 unrelated volunteers, also looking at their DNA (age 42 to
86, median age 63.5).
Participants were not excluded if they had
painful conditions such as osteoarthritis,
but they were excluded if they:
had taken painkillers within 12 hours of
the study visit
were likely to have problems with the
nerves of their arm – caused by
chemotherapy, stroke or known neuropathy (nerve pain), for instance
The researchers then analysed the DNA to
see if there was an association between
specific regions and the lower pain threshold. They tested whether any association
was dependent on other factors, such as
age.
What were the basic results? Nine regions
had changes in the level of DNA methylation. In the majority of the regions, the
level of methylation was higher in people
with a lower pain threshold.
The strongest association was in the "pain
gene" TRPA1. This was "hypermethylated" in individuals with low pain thresholds, meaning that this gene was less
active and much less able to "perform".
How did the researchers interpret the results? The researchers reported that they
had found "strong evidence for association
between DNA methylation levels and pain
sensitivity scores in a data set of 100 individuals". Conclusion
This study adds to the scientific knowledge about which genes play a role in pain
response. The study shows an association
between a low pain threshold and reduced
gene expression in nine locations on the
DNA.
This means that researchers have found
changes not only in genes already known
to be involved in pain response, but in
other genes as well. As the study was conducted in identical twins, the researchers
have also been able to identify that the
gene responses started off the same but
have become different for some reason.
The study shows that there is an association, but it does not provide information
about any medical conditions that the participants were suffering from or whether
any of the participants had chronic pain.
It is not clear why gene expression had reduced in these nine areas – the researchers
point out that the changes in levels of
methylation in the study either may contribute to pain sensitivity or arise as a consequence of pain.
This research did not l