Hi guys! If you read my blog consistently, you have probably heard me mention the International Association for the Study of Pain (IASP) before. I have been a part of this organization for just over a year now and I am in awe of all that this organization has done for the chronic pain community. A few days ago, I had the honor of interviewing its newest president, Dr. Andrew Rice. With over 35 years of experience in chronic pain research, he has a wealth of knowledge that I barely scratched the surface of in this interview. Read the interview to learn about the world of chronic pain research, IASP, diabetic neuropathy, post-amputation pain, pain after combat, and how research and healthcare systems need to change so that we can improve how chronic pain is treated.
Takeaways:
- Over the years we have gained a much better understanding of how pain works. Hopefully this knowledge will guide us towards better and more effective treatments in the future.
- When it comes to research, we need to place more value in rigor over novelty to ensure that our research is accurate and honest. We need to study the methodology behind each study before jumping to the conclusion.
- The International Association for the Study of Pain (IASP) is a professional society for people who study, treat, and teach about pain. It provides resources and advocacy all over the world for people working in the field of pain. IASP is working towards creating partnerships with those who have lived experiences with chronic pain.
- Neuropathy can be very difficult to treat. We have medications, but in the future we may transition towards treatments that are more psychological and behavioral focused.
Can you tell us a little bit about how you got involved in the field of pain medicine and research? Where did this journey start for you?
I graduated from medical school in London in 1982, just as the AIDs pandemic was starting. I was working at St. Mary’s at the time.
Anyway, I wasn’t sure where I wanted to go. I knew I didn’t want to be a surgeon. I certainly don’t have the skills for that. I was looking into various specialties, maybe anesthesia, intensive care, or internal medicine. I was doing a general medical rotation in a district hospital and was working on the oncology and palliative care service.
I met a young man with a Pancoast tumor, who was dying. This is a tumor at the top of the lung that eats into the brachial plexus (the nerves going down to the arm) and it is a very, very painful condition. He fascinated me because my boss, who was otherwise a very good and caring physician, would tend to avoid him on rounds. I think that was because he didn’t understand it and felt powerless to help, a scenario that Doctors are often not very good at dealing with. The reactions of some of the nurses interested me too because they felt that he was quite a demanding patient. He was demanding more doses of analgesia than was in their preset values.
I started to read and came across the writings of Patrick Wall, who was one of the greats of pain research in London. I went to talk to Pat and he showed me that in contrast to medicine, where pain is still something of a Cinderella area, that understanding pain was one of the most exciting topics in basic neuroscience. It’s an area of medicine that’s really on the edge. I like a bit of a challenge.
He advised me to go to a hospital in London called St. Thomas’s Hospital where they were starting a pain clinic. In fact, they were starting the first pain management programme in the UK. I applied for a job there and got it and I was then introduced to the neuroscientist Steve McMahon. If you want to read about Mac, please read the obituary we wrote in Pain for him about two years ago. He was an inspirational scientist, with an inquiring mind and unrelenting enthusiasm for research. He was a mentor to many other pain scientists. Unfortunately, he died a couple of years ago.
I went to work in his lab for my higher degree and he remained my key mentor and inspiration for the rest of his life. That’s how I got into this field. I had a chance meeting with a patient. That’s what I tell young physicians. You don’t have to have too many preconceived
ideas about what you want to do, but have your eyes and ears open and you may come across something absolutely fascinating you never thought you would have worked on before.
When you met this patient and you saw the pain that an oncology patient experiences, did this inspire you to go into the field of studying oncology pain or were you attracted to pain medicine in a more general sense?
More the latter. I found palliative care interesting. I had some great bosses there. At the time (it’s different now), it didn’t offer the same scope for research that other areas offered. What you have to remember is that pain medicine didn’t really exist then. It was a very new area.
Neurology was an option, but I was not smart enough to be a neurologist. Anesthesia was developing this specialty of pain medicine. I went into anesthesia, but only to do pain medicine. Later on, I went to Oxford to work clinically and they were generous and gave me plenty of time to continue my research with Mac.
There I came under some equally inspiring people that I can tell you about later if you’d like.
I would love that. You have been working in this field of pain medicine for over 35 years. What major changes have you seen in pain medicine over this course of time?
We have a lot more knowledge, but I’m not sure how much more progress we have made. I can divide my research career into two phases. One was when I was doing mainly laboratory or basic science and then in my early 50’s I reflected and I changed direction and focused on translational and clinical research and became interested in methods research and evidence appraisal.
Thanks to some remarkable neuroscientists, we now have a much better understanding of the basic science and a more understanding of pain mechanisms. You have already interviewed one of the greats of that area, Allan Basbaum, who was also a mentee of Pat Wall by the way. Of course, a major example is David Julius and Ardem Patapoutian recently winning the Nobel Prize for understanding how nerve cells transduced stimuli. They both gave plenary lectures at our recent World Congress in Amsterdam and were exceptionally generous in spending time with early career colleagues who I am sure found their interaction as stimulating as mine with Pat Wall and Steve McMahon.
The problem with this huge amount of knowledge is that by and large, we haven’t translated it into better treatments for patients and that’s frustrating. The area that has perhaps been more successful is in the area of psychology and behavioral aspects of chronic pain management.
The other area that has changed almost unrecognisably is our use of evidence. Two people who were inspirational when I worked at Oxford were Andrew Moore and Henry McQuay. They were disruptive in challenging the status quo in clinical pain management and pioneering evidence based medicine in the pain field . They made us look differently at the evidence we have and we have adopted into our clinical practice and policy the methods that they pioneered. We became much better at how we do trials. That’s revolutionized the way we think and the decisions we make and it’s probably had more impact on the clinic than anything else.
The cultural challenge in pain research, especially in laboratory science, is that the system places much more emphasis on “novelty” rather than rigor. We really want to shift this balance. This is how universities are assessed, how grants and publications are assessed, and how promotions and career progression are gained. Even if that “novelty” is very, very rarely translated into clinical practice. We should be rewarding well designed, conducted, analyzed, and openly published research which asks important questions informed by people with lived experience, irrespective of what the outcome is. If your methods are rigorous and the answer important then the outcome is important irrespective of whether the hypothesis being tested is proven or not.
I don’t like the term “negative results”, it is not helpful and it is stigmatizing. if the rigor is there and the question is important, then the results are important whichever way they turn out.
I’m a little bit newer to the area of research. I’ve just started getting into it myself a little. I work directly in a hospital and I like to read research that has been published on PubMed and other sources. I see really cool stuff that could help a lot of people. Then I go back over to the clinical setting and I see that we’re not actually putting into practice a lot of the new research that’s coming out. What are your thoughts on how we can actually get this research into healthcare settings so that it can actually benefit patients? What’s slowing us down here? Is there a lack of connection between those working in research and those working in clinical practice?
It’s more of a systemic problem and that is not unique to pain. The first thing I’m going to ask you is when you go to a journal and you see an exciting article, which part of it do you first read?
You’re probably going to hate this answer. I like to read the abstract which gives the overall description and then I skip down to the discussion and conclusion to see if there is anything that I can directly use. I’m not good at reading the methods yet.
You gave the usual answer, but also the wrong answer. You should go to the methods first because if a study doesn’t have sufficient methodological rigor that is transparently reported then it’s not worth reading.
One of the big issues is trying to decide which research we can trust. Someone I’d really like you to interview is Neil O’Connell, who’s also in the UK. We’re finishing a project (Entrust-PE) on what is meant by “trustworthy research” and this whole question of novelty versus rigor. I feel that in many areas of pain research the pendulum has swung too far in favor of novelty. However, we have too many novel experiments that can’t be replicated or translated.
If I give an example around drug treatments, for example, and I don’t by any means want to pretend that drug development is the only problem, but we’ll just take the example because it’s a good example of failed, and costly, translation. Virtually none of the drugs used to treat neuropathic pain have been developed by the traditional method of discovery in the laboratory. There are many reasons for that. We measure the simple but, unimportant outcomes in animal models, when we should be measuring much more complex behaviors that are impacted by pain. This is very difficult but it is encouraging how many bright minds are working on this throughout the world. It’s very much a case in the animal models of measuring what we can measure as opposed to what we should measure.
When you’re looking at a study and the methodology that was used in the study, what specific things are you looking for that identifies that this study was done in a way that is correct, accurate, and trustworthy?
Firstly I want you to do an interview with Neil O’Connell as he has really been focusing on this question.
The first step is that for hypothesis testing a protocol should be pre-registered and publically available. This discourages an activity called HARKing ( hypothesis after the results are known). The protocol should have a statistical analysis plan to discourage the practice of P hacking, which is when someone runs multiple different statistical tests until they find the one that gives the answer they want. That’s bad science.
There are aspects of study design and conduct which are critical to improving rigor in preclinical pain science and hence translation. Of course hypothesis testing studies must be randomized and blinded and that is becoming much more common. However, not reporting which animals were not included in the analysis and why they were left out is important and we have some way to go there. It is OK to leave data out of the analysis, but it needs to be reported and done on the basis of what exclusion criteria were declared beforehand in the study protocol. You should calculate the number of animals you need to use to produce meaningful results.
Sometimes it can be difficult to determine, for example when listening to someone present their results, to decide on how rigorously a study was conducted. I understand this as often one has only a short period of time to present one’s work and naturally we want to focus on the results and what they mean. Actually, I want to tell you about a great new initiative which will help this – some colleagues at NIH, have just come up with a bunch of rigor icons that you can put on your poster or slides showing which domains you have covered and demonstrate that you have done your experiment rigorously. I think it’s a really simple and useful tool. I do hope it becomes widely used, especially at conferences.
This is definitely good for me to know.
Actually, I’ll just say one other thing. Your background is in nursing, yes? I think you’ll find pain research a very welcoming environment because we tend to welcome people on the basis of what they do rather than what their professional background is. We’re very interdisciplinary in the pain field- it is central to our ethos.
I’d hope so. I was at the IASP conference in Amsterdam and I met a lot of amazing people there involved in the area of research and treating pain. I was constantly introducing myself as an ER nurse and most people were caught off guard by that. I had to point out to several people that we get a lot of chronic pain patients directly in our emergency rooms.
I am, sadly, not surprised to hear that. Often they don’t have anywhere else to go. I bet you see loads of people with back pain and sickle cell crisis too.
Yes, we get people with sickle cell crises, migraine attacks, arthritis, autoimmune flare ups, HIV pain, and post-amputation pain. We really get the full spectrum of chronic pain. I don’t think it’s very well known at this point that an ER is a great place to be interacting with a lot of chronic pain patients.
It shouldn’t be, but that’s the way it is.
Yeah, it’s definitely not ideal for the patients with chronic pain. If I could give a treatment outline to a patient of where to start, I would never tell them to start with the emergency room.
It’s also because they get a quick fix that gets them out of trouble for a few hours. That’s not, as you know, the long term management strategy we should be using.
It’s definitely not, but to transition to a different topic, I do want to talk about the IASP (International Association for the Study of Pain). You’re the president now. Congratulations on that. For my readers who have never heard of IASP before, what can you tell us about it? What does it do for research and the chronic pain community?
The IASP is a professional society for people who treat, study, and/or teach about pain. We are marking our 50th anniversary this year. IASP was founded in 1974 by John Bonica in Washington. If you were in Amsterdam, John Bonica’s children were there to help us celebrate. You would have heard about his work. We have somewhere north of 6500 members. We have 138 chapters and we just celebrated Armenia as our most recent chapter. We have 24 special interest groups that look at more detailed areas of pain. We have published PAIN which is the premier journal in the field.
We do a lot of global advocacy work, but a lot of that goes through the chapters. We often give our chapters the tools for them to advocate locally, although we do interact at a global level with the World Health Organization. You have probably heard of the US Pain Society Association, which is the new one. That’s our U.S. chapter.
That’s what IASP is and thank you for your kind words about the Presidency. It’s pretty daunting, actually, especially when I see the giants who have gone before me. I do get to decide a few things. I get to decide the next Global Year. We have a themed Global year every year and in 2025 that will be the year for pain research, education, and management in lower-middle income settings. That’s an interest of mine. I have been privileged to spend a lot of my working life learning from colleagues in lower-middle income settings, particularly in South Asia and Southeast Asia.
We have also just announced two new task forces:
One will update our guidelines on the use of laboratory animals in pain research which are now over 40 years old and need revising. This taskforce will address many of the experimental issues we discussed just now.
The other task force will examine environmental sustainability. Firstly we will examine IASP’s institutional environmental footprint and explore ways of mitigating that. Secondly, we will identify where the environmental impact of the clinical and research activities of IASP members might be improved. For example we might look at how we can use less plastics in laboratories. Waste water pollution by analgesic drugs is a major problem that’s not fully recognized yet.
And if you haven’t heard of us, that is a problem we are already actively doing something about. We’ve always been a professional society and we need to improve how we interact with people with lived experience of pain. I’ve always encouraged basic scientists in particular to go and interact with patients and this was also started by the previous president. I really want to ensure that we have the lived experience voice central to our beliefs. I want more people to have heard of IASP in two years time because we will have a louder voice.
What we don’t want is to become an advocacy group. There are plenty of those for particular diseases, but we want to have the lived experience absolutely central to everything we do. We have a long way to go. We have these voices on most of our committees and things like that, but we need to formalize it and take it a lot further forward. That goes for research as well as clinical practice .
When I first became interested in the field of pain medicine and I started doing these interviews, I quickly discovered that a lot of the people I was interviewing had at one point in time, experienced chronic pain themselves. I think the opportunity is definitely there.
Yes, we want to have a partnership. Something that is a bit more than just participating. Some people like to say “Don’t talk about us without us” in regards to those with chronic pain. And it saddens me that a lot of people don’t know about us, but it tells me we’re doing the right thing. We need to up our game in that area.
The way I discovered IASP was directly through one of my interviews. It was with Dr. Andrea Furlan. She was the first one who told me about it. I saw at the conference that she had done a study on including someone with lived pain experience on a pain medicine team. I thought that was very interesting. I really liked that study.
I want to transition now and talk about your research which covers a broad span of topics. I tried to focus the questions a little bit because I feel like this interview could go on for hours if we try to cover all of the topics. I was looking specifically at types of chronic pain that I see in the emergency room.
One of the most common symptoms I see in the ER is diabetic neuropathy. It’s very common. Can you explain what it is and how diabetes leads to it?
Diabetic neuropathy is nerve damage from diabetes. There are actually many different types of nerve damage in diabetes, but the predominant one is what we call “length dependent distal symmetrical polyneuropathy”. This means your longest nerves are the ones that are the most affected and generally people feel symptoms in their feet and hands first.
Obviously diabetes is one of the most important healthcare threats we face and it’s going to increase.
We don’t really understand precisely what causes diabetic neuropathy. It’s one of a many complications of diabetes such as eye damage, liver problems, and kidney damage. We think it has something to do with the small vessels that supply the nerves. These vessels become clogged up and the nerves start dying. They die from the skin backwards which is why the longest nerves are the most commonly affected.
Diabetic neuropathy is one of many conditions associated with neuropathic pain or pain from nerve damage. It usually manifests in other sensory symptoms as well as pain. Patients often experience numbness where they have their pain. That’s counterintuitive to physicians and patients. How can someone have pain where they are feeling numb? But that’s exactly what it is. They can also experience electric shocks of pain or hypersensitivity. But the most common features are pain and numbness.
There are animal models of diabetic neuropathy, but they don’t reflect the pain component. They reflect what we call sensory gain or this sensitivity that some patients get.
We don’t know how to prevent it. There’s no disease modifying therapies other than taking very good care of your glycemic control. We have a number of drugs that help with the symptoms and we can come back to those. They’re not as effective as we would like.
It’s a huge problem and I am working with David Bennett at Oxford and other colleagues in PainStorm (www.painstorm.co.uk) and we’re trying to drill down into all of the aspects of what characterizes a patient with painful diabetic neuropathy. We’re looking at their genetic profile, sensory profiles, psychology, and quality of life. That kind of multidisciplinary research is yielding quite a lot of good answers, but we still don’t have a disease modifying therapy. A major advance in preventing neuropathic conditions is in preventing postherpetic neuralgia because we now have an effective shingles vaccine .
As far as treatment for diabetic neuropathy goes, what are the most successful treatment options being offered to patients?
I would emphasize that we don’t have treatments that modify the course of diabetic neuropathy other than taking good care of your blood sugar over the long term. We have drugs that are used in the treatment of epilepsy or depression like gabapentin or pregabalin. We have antidepressants like amitriptyline. They are effective in clinical trials and they work for some patients, but not all. But I’ve got to be brutally honest, for most patients, these medications don’t work. They work for less patients than they do work for so we celebrate those small successes. We’re very aware that they don’t work for most patients and that they have side effects. The challenge is to see who’s going to respond to amitriptyline, who’s going to respond to duloxetine, and who’s going to respond to pregabalin. One thing we know that absolutely doesn’t work is cannabis and cannabinoids. We’re absolutely certain of that despite what you might read in the newspapers.
Do we understand why it is that some patients respond very well to medications like gabapentin and pregabalin and other patients don’t respond to these medications?
We’re not sure yet. We’re doing research to find out the differences in patients to try and predict that, but it’s just a hypothesis at the moment. The one thing we have ignored and it’s a soapbox of mine, is multidisciplinary behavioral type treatments like cognitive behavioral therapies specifically for neuropathic pain. They are much more established for musculoskeletal pain like back pain. Whitney Scott is a psychologist that works in London. She and some other researchers asked some people living with HIV what their symptoms were and what really bothered them and then designed a program specifically for them. The feasibility testing went quite well.
I feel like it is a growing area of treatment, at least in the United States. We are definitely starting to have more and more programs that are offering psychological interventions for a lot of different types of chronic pain. The downside is that they are often expensive and not very accessible to a lot of patients.
There’s a lot of work going on, particularly with modern virtual technology to make these services more accessible.the problem is that they’re expensive. If you listen to the interview on Pain Research Forum by John Loeser (one of the founders of IASP), he’ll tell you why it is difficult to establish these programs in the U.S. healthcare system. He doesn’t hold back. The other problem with these programs is that they are designed for the needs of people with musculoskeletal conditions like back pain. They’re very geared to physical activity parameters but these may not be so relevant to people living with neuropathic pain.
You have also done research on post-amputation pain which is another condition that I see on a regular basis, either due to trauma, diabetes, or cancer. How does post-amputation pain develop? How is it possible for someone to feel pain in a limb that isn’t even there?
First, I want to take one step back and say that post amputation pain is a new area for us. Most of my research has been in the context of nerve damage like neuropathy, infectious diseases, HIV, shingles, and leprosy in particular. This is quite a good example because people say “how can you feel pain in leprosy? Isn’t it a painless disease?” No, they lose their sensation, but 25% of them experience pain.
Going back to post amputation pain, it is more than phantom limb pain because you can also have pain in the stump. It’s really important to differentiate those two aspects. Most people who get an amputation will have a phantom but it’s often not painful. It might be distressing. For around 20-30% of them it is painful.
To study this, we took an unusual approach. I’m an amateur historian and I worked with a historian in my research group. That’s real interdisciplinary work. So we went back to the biggest amputee cohort in history and that’s from the First World War. There were 42,000 veterans with amputations in Britain and greater numbers in France and Germany. There were many more in Russia. These were by and large men who had lost their limbs in their 20s. These men had never been studied in any longitudinal study. So we went to the National Archives in Britain and looked at their pension records which had been released in 2016. They were not publicly available before that. In this research we identified what we called “cycles of learning”. This was where an idea, usually a surgical idea, for managing post amputation pain would come up and then it would be abandoned because it didn’t work and then 20 years later someone would reinvent it and repeat the process. This went on and on for several decades.
We have not become much better at treating post-amputation limb pain and there are a number of areas where knowledge has advanced considerably. You only need to look at the Paralympic Games. For instance, there have been fantastic advances in prostheses. It’s just unbelievable when it’s compared to the wooden and metal prosthetics someone would have had after the First World War.
One of the things that slowed us down was that they didn’t start regularly asking about post-amputation pain until the 1950s. They recognised it earlier on because the earliest accounts in 1915 said that they had to be managed by multidisciplinary teams. Most people think multidisciplinary treatment came around in the 1980s or 90s. Yet they were talking about it in 1915. People with amputations didn’t talk about or describe their pain. It was a hidden disability. You can see that someone has a missing leg, but you can’t see their pain. That’s very common for people living with chronic pain.
Nothing much happened and we’ve gone through 100 years in that stage without really improving on the act. We have looked at 20th century accounts of the Vietnam War, and other wars. What we have shown recently is whilst many people with amputations report some pain, but for most people that pain is relatively mild and they live with it. But for around 20-25% of people, it’s a very significant pain that has a lot of impact on their quality of life and social interactions .
We have now moved this work on to a new phase and are thrilled to be working with the ADVANCE Study (www.advancestudydmrc.org.uk). This cohort is following up for about 20 years about 600 British servicemen together with matched control and will be studied. They’re all men injured in Afghanistan in the recent campaigns there and they are already giving us very valuable data. We’re optimistic that we’re going to find some things that will help us understand this problem better.
We want to try and understand why one person is severely impact by chronic pain and another isn’t even if they have the same injury. I think that once we get to grips with that, we’ll start to make some advances.
When we’re working with these patients who have pain after combat, would you say that there is a strong relationship with PTSD or mental health problems and chronic pain?
Probably, but we haven’t analyzed that data yet. It’s too early for me to answer that. I think we need to delve down into that. The truth is that all three of those problems are prevalent in post combat, but we need to know whether they’re perhaps equally prevalent in civilians who have been through similar traumatic events. So I’m going to push that question to the side because we simply don’t know the answer yet.
I’d like to wrap this interview up with one last question now. What are changes that you would like to see both within healthcare systems and research for treating chronic pain?
I’ll probably be long gone by the time I can be proved right or wrong, but the first big change I would like to see is increasing involvement of those with lived experience in co-creation of both our research and clinical programs. I think that will be something that really helps us advance. They have really educated us as to how individual and complex people’s pain experiences are and how they have to deal with their pain on a background of their underlying disease. Every patient is different. An 80 year old lady who’s had an amputation due to vascular problems does not have the same issues as a 23 year old who lost a limb in an explosion in Iraq.
Working with people who have lived experience in designing our clinical interventions is critical to success. At the World Congress in Amsterdam I was really excited to learn about some work in New Zealand. Our colleagues in Otago have co created with Maori population pain management approaches that are appropriate for the needs and culture of the Maori community
After nearly 40 years of research, I’ve finally learned that pain is complicated. For many types of chronic pain I really think we’re going to have to move on from magic bullets and quick fixes with injections, drugs, and other stuff. They are not the answer for most people in chronic pain. They might be part of the answer. We need to be better at combining treatments.
I think we’ll probably shift much more to behavioral type interventions. Healthcare providers don’t like that because it’s expensive and it’s very human resource intensive. We can improve on some of that with virtual programs.
Michael Nicholas who’s in Sydney, Australia wrote a really good paper on optimizing care pathways for chronic pain.
Currently we generally practice stratified care whereby patients work through a pathway usually starting with the most accessible and cheapest options. Those who are failed by one option generally pass up to the next stage, but that means that the patients who do not benefit from one intervention then go on to the next expensive intervention, this is not efficient. Matched care is an alternative concept where we try to understand the needs of individual patients and match them to appropriate care right from the start. He tested this in people with musculoskeletal pain in a worker’s compensation setting . What they did is they identified people with back pain who were showing early signs that they weren’t going to do well and they took these people into another program that was more psychological or behavioral intensive. And their results were astounding and they prevented a lot of people from developing chronic pain. So earlier interventions and match care is something that we like.
Next is we have to be courageous. We have placed a lot of faith in therapies that don’t really work. We have to be courageous and ditch them because sometimes they can be harmful. I’m particularly worried about cannabis because we know it doesn’t work for most pain conditions and it has the potential to cause harm. There are all sorts of interventions for back pain that we have very poor evidence for yet we continue to do them.
The other thing that we have already talked about is the impact of bias in research results by having more emphasis on novelty and originality than we have on rigor. Valuing novelty over rigor means that we’re wasting huge amounts of money by letting drugs through clinical trials that should never have got there. We’re not filtering them out. We need more trustworthiness in research.
Huge thanks to Dr. Andrew Rice for doing this interview with me. Check out IASP to learn more about medicine and where the current research is taking us. https://www.iasp-pain.org/
Interesting and inspirational – thank you, Linda (chronic migraine person).