Can you tell us a little about your background and how you got into this field of medicine?

I am a rheumatologist by training and the thing that attracted me into rheumatology in the first place was the diversity of the conditions and the diseases that you see and that these conditions most often affect so many other parts of the body. I always thought that was really fascinating and I loved going to clinics where you would see doctors actually trying to piece together the different bits of evidence and the different test results from all the different parts of the body. It was a bit like detective work which I thought was really fun. I also liked the idea of thinking about the whole person because medicine can sometimes be super specialized, whereas I felt with rheumatology it’s really important to think about the whole person.

In terms of how I got into osteoarthritis and pain, I think the main influencer there is Professor Paul. I think many would say that he is the godfather of rheumatology. He wrote the textbook for rheumatology that everyone reads when they’re training. I went to a talk that he was giving at the Royal College of Physicians. It was a whole day of talks about osteoarthritis and rheumatology in older individuals. He basically stood up and introduced himself as an ex-rheumatologist and a grumpy old man and I thought, “What’s going on here?” This is the guy who everyone looks up to for rheumatology. He went on to explain that the reason for that is that he felt like the specialty had lost the plot and was far too focused on all the immunology and inflammatory conditions. He felt that we had forgotten about really common problems like osteoarthritis which affects so many of us and leads to pain, disability, and a poor quality of life. In his opinion, rheumatologists weren’t really focusing on what was important so that’s what inspired me when I was considering topics for my PhD.

I was fortunate at that time because Professor Irene Tracy, who is here in Oxford and known as the Queen of Pain, took me under her wing and I joined some of her pain group meetings and I was inspired by and really interested in the neuroimaging work that she was doing. That’s how I ended up focusing on brain-mediated processes involved in common rheumatic conditions such as osteoarthritis and then more recently rheumatoid arthritis and fibromyalgia.

I see that you have done research on abnormal pain central processing in patients with knee osteoarthritis. Could you explain what pain central processing is?

This involves thinking about the central nervous system which includes the brain, brainstem, and spinal cord. Those are the central structures that we are referring to when we’re talking about pain processing.

Osteoarthritis was typically thought of as being a very peripheral pain problem because the joint is damaged. The assumption was always that there’s something in the periphery that damaged the joint and that must be generating the pain signals. In actual fact, research we have done has shown that for some people there is this abnormal centrally mediated pain process. This pain processing contributes to that pain experience so that someone may become sensitized to things like light touch or light pressure which you wouldn’t normally expect to cause pain or discomfort. It’s almost as though the volume has been turned up on their pain sensors and we know that is happening within the brain itself. Those signals coming in from the periphery are actually being modulated and amplified by the brain.

In reality, the brain is what determines the pain experience. It takes all the information that it gets from the outside world, but also uses information that it has from past experiences, previous memories, and the amount of sleep that someone is getting. All these features culminate in the pain experience that someone goes through. It differs between individuals, but it can change from day to day, even if that person’s circumstances have not changed.

Can you explain how knee osteoarthritis is leading to pain central processing and how long it takes to develop?

We used to think that it happened after many years of someone experiencing constant nociceptive signals coming in from damaged joints. However, there have been other studies that have shown that people with evidence of central sensitization haven’t necessarily had their osteoarthritis longer than people who don’t have features of central sensitization. That would go against the theory that it’s a time-dependent factor.

An area that is becoming increasingly recognized is the concept of pain vulnerability. There may be other factors about an individual that put them at a higher risk of developing pain central sensitization. It’s not fully understood yet but the factors may range from genetic profile, environmental triggers, and early childhood experiences. These factors can add extra insult to the pain that is experienced with osteoarthritis.

How do you determine that someone has abnormal pain central processing and that their pain isn’t purely structural and peripheral?

It’s really hard and I think there’s still a tendency to assume that when we see really bad x-rays, for example, that show very marked joint narrowing and lots of damage to the cartilage that that must be what’s driving the person’s pain. But the clues are there. You have to zoom out a little bit and think about the person as a whole. If somebody has more widespread pain then that is usually the biggest clue that there may be central sensitization present. Non-pain features can also be helpful. These are things like disabling fatigue, sleep disturbance, and sensitivity to things like sounds. Sensitivity to light touch that can be anywhere in the body and not just the affected joint is another sign.

There are also some questionnaires that have been used mostly in the research setting that have also been helpful. For example, in a study that I did, we used a questionnaire called the Pain Detect because at that point that was the one that seemed to have the best evidence. Our imaging showed that it could indeed pick up some of the people with pain centralization. 

Since then there has also been a fibromyalgia score that’s been developed which is based on the 2016 American College of Rheumatology criteria. That can be used to continuously measure the degree of widespreadness of pain and other non-pain features that were mentioned earlier. That continuous measure can give you a clue as to where a person might be on the scale of central sensitization scale. These are the sorts of tools that we have available, but I think it’s fair to say that the jury’s out still and there isn’t a clear way in clinical practice of determining if someone has abnormal central processing yet.

Do you know if there is anything that can be done to prevent abnormal pain central processing?

I don’t think I am aware of anything that has been proven because if you think about the study that would have to be done, we would have to identify people before they developed the central sensitization, implement an intervention, and then show that it worked compared to people who didn’t use interventions. I’m not aware of any studies doing that early on, but I think that would be an effective thing to try and do.

There are studies looking at people further down the line. For example, if they have had knee replacement surgery and they still have pain, there have been interventions to try and help them in that scenario, but I’m not aware of anything more upstream.

The closest we can get is to look at the epidemiology studies that point to risk factors for developing central sensitization type pain. Those are things like sleep disturbance, mood disturbance, and other modifiable potentials.

The other thing that has been looked at in the context of knee replacement surgery is something called prehabilitation. Rather than waiting for them to have their surgery, we can have them build up the muscle strength and mobility as best they can before the surgery. This way they’re in an optimized position and at a lower risk of developing persistent pain. There’s certainly evidence to support that, but I do believe that you have identified a gap in the literature.

How does abnormal central pain processing impact the treatment for knee osteoarthritis?

The people who we identified as having abnormal pain central processing still benefited from surgery. The key thing to note is that they didn’t get the same level of benefit compared to people who didn’t have the features of central sensitization. There are currently studies looking to see whether treatments prior to surgery can help improve people’s outcome. We’re trying to determine whether drug intervention can actually shift the graph so that those people with central sensitization get to the same level of quality life after surgery as the people who do not have central sensitization.

What is the treatment approach once someone has had the surgery but they are still experiencing high levels of pain?

The approach at that point from a clinical perspective is zooming out and taking as much of a holistic approach as you can. You have to think about how well someone is sleeping, how much movement they’re doing, are they scared to move, and has the pain impacted their mood? It’s really about all of those factors as well as working closely with the surgeons to make sure that the surgery went well and that from a purely structural perspective that there isn’t anything else that needs to be done. 

There’s a trap where people can potentially end up having revision surgery when there’s actually no indication and that can actually make things worse. Part of the approach is being very careful about any repeat surgery and only going back in if you absolutely have to. Other than that, it’s mostly about taking a non-interventional approach and offering a holistic rehabilitation style. 

We’re very lucky here because we have a wonderful pain rehabilitation program and a lot of those patients will be referred to a program that’s overseen by a physiotherapist who is well versed in the psychological approaches to treating pain. Sometimes they are referred to a program led by a psychologist. There’s a lot of cross fertilization in terms of approaches and it’s all about helping people to understand the neuroscience behind pain. We help people understand how different medications work and why medications on their own may not be sufficient. We given them support and guidance in feeling confident when they are doing exercises and movements, as well as information about sleep hygiene. We can do mindfulness, goal setting, pacing and so on.

When you think about how a medication works, it’s only going to affect one very small aspect of the whole interconnected series of pathways, neurons, and neurotransmitters. There’s no way that a medication is ever going to be able to cure everything. I think the only way to intervene is to use as many strategies as there are available to really help.

Doctors haven’t necessarily had that kind of training. I think this is a relatively new concept that hasn’t yet been taught to everyone. In medical school, we have very little time where students are taught about chronic pain and how that differs from acute pain and the approaches to managing it. I think that gap is still there as we progress in our training. There is a gap there, but also the infrastructure of the health service doesn’t lend itself very well to trying to do that. We’re quite lucky here in Oxford because we have a pay network set up within the trusts. Once or twice year everyone who is in the trust comes together and it’s really valuable for everyone to be aware of who is managing which conditions and how they’re doing it. If it weren’t for that network, it wouldn’t happen naturally because why else would you get gynecologists sitting next to neurologists sitting next to rheumatologists sitting next to anesthetists sitting with psychologists and pharmacists? There is no other reason that all of those people would be there in one room. The discussion is amazing and there’s lots of sharing and brainstorming together. There are also researchers and it’s great for them to see how their work translates over into the clinical world.

I noticed that you’ve been involved in research for fibromyalgia. Could you talk about the neurobiological causes of fibromyalgia and how they impact treatment?

Each person who presents with the symptoms and signs of fibromyalgia is different. There is huge heterogeneity between cases. I don’t believe that there’s just one cause and that it’s all stress and psychologically based when there’s a whole host of potential triggers and factors. I would say it’s impossible at an individual level to unpick those factors, but they range from a person’s genetic profile to things in the environment as well as previous experiences with pain.

There are two main ways of thinking about fibromyalgia. Dan Claw, who has done a lot of work in this field would describe a top down scenario. This is where it’s coming from the way the brain is processing painful signals. Then there is a bottom up version which is where there is a peripheral trigger that is driving the neurobiology to act in the way that it does.

The common factor that is seen in people with fibromyalgia is altered connectivity between important areas of the pain processing system. The descending pain modulatory system is dysfunctional and everything is amplified. This is probably why people experience more persistent and diffuse pain. There are very clear differences that have been shown time and time again, that if you present the exact same stimulus, it’s all calibrated. We can see this with neuroimaging of the brain. There are differences between people who are living with fibromyalgia versus pain free and healthy individuals.

Where do you think the research on both fibromyalgia and osteoarthritis of the knee is taking us within the next five years?

I think it’s a really exciting time to be in this field from the research side, because it has gained traction so there’s more funding being put into researching these conditions. People are recognizing that we need to think about pain as separate from the inflammation and structural problems. Once you have couples funding with motivated research, we should be seeing new approaches and new technology being used in novel ways.

Neuroimaging allows us to dive deep into individual brain responses rather than having to look at it on a group level which is what we have traditionally done. Once we can try and unpick mechanisms for an individual we can start to tailor the treatment which is the ultimate goal. I think the main reason that treatments have generally poor results is because we’ve been trying to treat everyone the same way. 

It probably isn’t realistic that we want to scan everyone’s brains before we give treatment in a clinical setting. There is a translational work where neuroimaging can help us understand which questionnaires and screening tools work best.

There are also some really clever techniques coming out such as virtual reality and tools that can help retrain people to gain confidence with movement. Advances in technology are becoming more accessible to people. One of the bits of work that we’re doing is looking at a digital form of cognitive behavioral therapy that targets insomnia. It’s basically a digital professor with an algorithm. According to how you respond, the app updates the algorithm and gives different lessons. One of the massive limitations in healthcare is the lack of resources and people that are available to provide training sessions of CBT. The app could be more effective than working with a therapist and it’s accessible to so many people at a much lower cost.

Covid forced us to look at different ways to communicate with our patients because we could no longer assume that they can come in physically to see us. So we designed a pre-clinic and mini assessment form. We could send the link using microsoft forms and people could fill out questionnaires before they even came to the clinic which was really helpful to have the opportunity to ask them what they have tried already and what they would like to focus on in the consultation. When they came to the appointment we already had loads of information about them and we could use the time together to focus on the important things.

In your personal opinion, what do you believe is the best way to treat osteoarthritis of the knee and also the best way to treat fibromyalgia?

For both of those conditions, the key is to assess the patient and not just their painful knee, and to think about them as a whole person. In terms of osteoarthritis, surgery really works well. You need to understand how their condition is affecting their quality of life. It’s also a case of not relying on any one thing, but thinking about all the different ways that you can optimize a person’s recovery process. You have to think about the other factors that are contributing to a person’s pain. You have to consider their sleep habits, mood, and activity levels and make sure that people are aware that even if it’s causing pain, it doesn’t necessarily mean that they’re damaging their joints or causing any structural long-term damage. Exercise and building muscle strength are really important.

For the final question, is there anything that you would like people to be aware of?

I want to share hope because we have reached an exciting time where people are recognizing the importance of considering chronic pain in its own right and not just a byproduct of another condition. Progress is slow, but we are definitely moving in the right direction. I want my colleagues to remember to think about the whole person because sometimes those non-pain symptoms give us a way to help that person.

Takeaways:

• The brain determines the pain experience. It differs between individuals and can change each day.

• It is difficult to determine if someone has abnormal pain central processing, but there are signs. These include widespread pain, disabling fatigue, sleep disturbance, and sensitivity to sounds or light touch.

• Prehabilitation can be done before knee replacement surgery. This involves building up muscle strength and mobility prior to surgery. This can lower the risk of persistent pain after surgery.

• Surgery is an effective way to treat osteoarthritis of the knee, but we also have to consider sleep habits, mood, and activity levels.

• We have to think about the whole person when treating chronic pain.

A huge thank you to Dr. Anushka Toni for doing this interview with me. I learned so much from her and I’m excited to see her research impact the chronic pain community. She is making a huge difference to those with osteoarthritis of the knee and fibromyalgia.

Hang onto Hope!