Wednesday February 5 2014
Pain thresholds aren't just a figment of the imagination
"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 study of 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".
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 look at whether this methylation could be reversed or if it would change the experience of pain, so the prospect of any new painkiller stemming from this research is a long way off.
Talk to your GP if you are finding your quality of life adversely affected by pain. They may be able to refer you to an NHS pain clinic. Pain clinics vary, but usually offer a variety of treatments aimed at relieving long-term pain, such as painkilling drugs, injections, hypnotherapy and acupuncture.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.