Caroline Hayward: How can we use genetic techniques to understand chronic pain?

Caroline Hayward: Image courtesy of Caroline Hayward

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Let’s dig a little deeper into how researchers are trying to join the dots between genetics and  pain. Professor Caroline Hayward and her team at the MRC Human Genetics Unit, within the Institute of Genetics and Cancer, have been working together with clinical colleagues like Blair Smith, scanning through the DNA from thousands of people in the Generation Scotland study and other cohorts in search of genetic variations that might be contributing to chronic pain. So, how does she do it? 

Caroline: Well, the phenotype, which is the definition you're using for pain. And if somebody has chronic back pain, which has lasted for a long time, they will be basically a case. And you have controls who have not had any pain and you related to age and sex. And you correct for that because obviously, as you get older, you have more pain. So we do genome wide analysis, which is looking at the whole genome and we can identify the regions that are associated with people who have pain compared with people who don't have pain. And you will see differences in the genetic components.

Kat: Might sound a bit strange that you're trying to find genetic variations that are associated with something that, certainly I think, is quite physical. Like maybe someone's had an accident or they're not sitting properly at their desk, or they've lifted a box funny, or they're just getting old and creaky. So do we have any inkling that the genes will be involved in some way? What gives you hope that there might be some kind of connection?

Caroline: Well, we know there is some influence of age and sex relating to pain. We know that, but also we know that there must be some genetic component to this because people have looked at family studies and you do have a tendency to get different generations who have very similar things. You have things like rheumatic pain and rheumatism and things like that, which are pain related factors. And I think there is inevitably with all things there's likely to be genes involved, but unfortunately it's very, very difficult because pain is not just one thing, it's a very diverse set of conditions.

Caroline: So by getting large enough numbers of individuals, you hopefully can pull out or tease out the actual genetic influence. The genetic influence may not be that high. It's very diverse, very, very, very diverse phenotype, but there is slow progress there is progress. And certainly with the UK Biobank, they have something like nearly half a million people of which they've got substantial numbers of cases and controls, and they are actually starting to identify things.

Caroline: But again, it's how you define pain and you can do it by specific locations, but that may not be relevant. And there may be some psychological aspect of pain as well. And certainly there has been a study relating to depression and pain. And people there have found that there is some association with the risk of developing depression and pain. Now whether you develop depression because you have pain or whether you have pain because you have depression, it hasn't been untangled.

Kat: I can see that it does seem like a very complex problem because, on the superficial level, you can imagine that there are genetic variations that contribute to how your skeleton is built, how your tendons fit together, how your muscles work, your arm's slightly wonky or something like that. And then the genetic variations that affect how much you are sensitive to pain are you someone who's like, Ooh, that hurts a lot. And then, like you say, the psychological side of it and how your brain is kind of wired up and working and all sorts of other influences that fit together. It does sound like a hard problem. So that I guess the scale of the number of people and the number of places in the genome you need to look at, how do you really go about trying to get the scale of the data that you need to find these associations?

Caroline: Well, you have to collect the data and you have to collect the samples and people have, to have asked the correct questions in the cohorts. Now there's lots of big cohorts across the world, internationally, there's a Japanese cohort. But some of these have not asked the specific questions and there are pain questionnaires that are defined specifically from a clinical point of view to actually hone in on pain itself.

Kat: Yeah I guess if you're not defining it in a standardised way, then you can't get standardised insights out of it, even if all your other things are the same.

Caroline: Yes, that's exactly it. It's very difficult. And there are quite a lot of other conditions that are very much the same. And ME is a classic example. It's a whole range from right across maybe there might be a hundred, two hundred, even more different forms of the same thing and pain may well come into that sort of thing, which makes it very, very difficult. But it's still worthwhile and with bigger sample sizes, it will become more and more possible to actually focus in to what is important.

Kat: That’s Caroline Hayward, from the MRC Human Genetics Unit. Thanks to my other guests, Blair Smith, Andy Devereux-Cooke and Chris Ponting. And also thanks to the Institute of Genetics and Cancer at the University of Edinburgh for supporting this episode, and to Dee Davison for setting it all up.