Seven early-career pain researchers took part in the PRF Correspondents Program during the 7th International Congress on Neuropathic Pain (NeuPSIG 2019), which took place May 9-11, 2019, in London, UK. This unique science communications training program provides participants with knowledge and skills needed to communicate science effectively to a wide range of pain researchers and to patients and the broader public. In addition to blogging and writing summaries of scientific sessions, the Correspondents also conducted interviews with plenary speakers. At NeuPSIG, PRF Correspondent Brenda Dyal, PhD, DNP, a postdoctoral associate at the University of Florida, Gainesville, US, spoke with NeuPSIG plenary speaker Lesley Colvin, MBChB, PhD, for an interview.
Colvin is Chair of Pain Medicine in the Division of Population Health and Genomics at the University of Dundee, Scotland, UK. Her specific research interests being developed in Dundee include pain assessment and vulnerability to chronic pain, opioids in chronic pain, pain and addiction, chemotherapy-induced peripheral neuropathy (CIPN) and other neuropathic pain conditions, and cancer-related bone pain. Here, she discusses how she developed an interest in CIPN, the role of opioids in the treatment of neuropathic pain, and much more. Below is an edited transcript of the conversation.
What led you to spend your career on the study of pain?
I’m an anesthetist by training, and during my training I became very interested in the physiology and pharmacology of pain and how we managed it because it is such a major clinical challenge. I took time out of anesthetics school and worked in a lab with Professor Arthur Duggan, who was my supervisor, and I spent three years trying to understand the spinal mechanisms of neuropathic pain. I then went back and finished my training in anesthetics, and during that time specialized in pain medicine, which is what I do all the time now.
How did you become interested in chemotherapy-induced peripheral neuropathy (CIPN)?
That’s a good question. My PhD was in neuropathic pain, and I’ve always had a particular interest in neuropathic pain. In my clinical practice, I did for many years a combined clinic with palliative care in the Edinburgh Cancer Centre, where we saw many patients with cancer pain, but also, more and more over time, with cancer treatment-related pain.
CIPN in particular has become an increasingly significant problem over the years that I’ve worked in clinic. It struck me week after week that the patients we saw there were hugely disabled, in terms of their quality of life, from the treatment that often cured them of their cancer, but we really didn’t have any effective therapies to offer them. That’s how I became interested in CIPN.
You recently published in PAIN an article titled “Chemotherapy-induced peripheral neuropathy: where are we now?” There you discuss the role of genetic factors in CIPN. What do we know about this area?
It’s part of the effort to understand the genotype and phenotype of individuals in order to link their signs and symptoms to underlying mechanisms, including genetic factors, so we can stratify our treatment approaches and, ideally, individualize those approaches. As I mentioned in my lecture this morning, one of the issues is that everyone gets a standard dose of chemotherapy, and it’s only altered if there is a problem, as in the case, for instance, of CIPN.
What I think oncologists need to be doing and would like to do is better understand the toxicity of treatments so that they can individualize them. In cancer medicine we are now using genetics to direct treatment in terms of chemotherapy and immunomodulators, but we’re not there yet in terms of understanding toxicity and perhaps managing CIPN. So that’s one direction that will be interesting to explore further.
Also, there are healthcare databases and research databases, such as the UK Biobank, which contain patient information including blood samples, imaging, and phenotyping of patients in terms of their pain profile; patients can sign up to participate in these databases. So we are beginning to have the opportunity to have large enough patient populations so that we can start to look at the genetics in a bit more detail and get something meaningful out of it.
Within Scotland we also have some interesting opportunities with an initiative called SHARE, which is the Scottish Health Research Register. People can sign up online, and doing so gives consent so that if you’re a patient in any National Health Service (NHS) system within Scotland, your data can be used, and if you have any stored blood, that can be used, and you can be contacted for potentially relevant research studies. That’s a huge database for the genotyping that is beginning to go on within SHARE. The SHARE database has about 250,000 to 260,000 individuals signed up to it, so it’s a hugely powerful resource.
What we can also do in Scotland, if an individual who has contact with the healthcare system has a unique identifier, called the CHI number, is link the data from SHARE with national prescribing data, for instance. So potentially you could look at individuals with cancer, the chemotherapy they’ve had, and then other comorbidities and also the genetics.
What is the role of patient education in understanding risk factors for CIPN as well as treatment approaches, whether pharmacologic or non-pharmacologic?
Patient education throughout the cancer journey is really important, because if you get a diagnosis of cancer, it turns your life upside down. Many individuals say that they receive a diagnosis and a whole load of information about potential treatment options, but it’s such a difficult time to actually take in that information and make the right decisions about treatment.
Delivering education at the right time and in the right way to allow patients to make an informed decision about oncological treatment they might choose is necessary. If you’re going for chemotherapy, having an understanding of risks and benefits is important. If you’re in one of the high-risk groups to develop CIPN to the extent where you’re so miserable that life is not worth living, the risk/benefit analysis for you as an individual is quite different from someone who’s at very low risk of developing very unpleasant side effects. So we are beginning to understand who is vulnerable, what the risk factors are, and how to use this for patient education and informed choice.
In terms of managing pain, patient education and understanding of pain is important. In addition to using pharmacological therapies, psychological techniques are valuable; we know there’s evidence that they are effective in the management of chronic pain.
What are your thoughts about the use of opioids in the treatment of neuropathic pain?
We had to discuss opioids at some point.
We did, didn’t we?
Well, you’re from the States, and clearly there is concern there, particularly about the increase in prescribing of opioids. We’ve looked at this issue within Scotland, and from 2003 to 2013 there was a doubling of opioid prescribing. In 2012, which was the year that we focused on in particular to find a bit more detail about why that might be, 18% of the Scottish population were prescribed some form of opioid, which is a huge number of individuals.
So, should we be using opioids for neuropathic pain? If you look at the neuropathic pain NeuPSIG guidelines, opioids are there but they are quite far down the list; they’re known as third-line therapy. The current climate in the States is that opioids are good analgesics but we need to use them properly and ensure that if we’re using them, the risks and the benefits must be balanced.
There was one randomized controlled trial published in JAMA last year that looked at randomizing to opioid or non-opioid analgesia, and followed individuals out for a year; this was for osteoarthritis and for back pain. Patients who were on strong opioids had worse pain, so there was actually a downside to being on a strong opioid.
We do know from our understanding of the mechanisms of neuropathic pain that mu opioid receptors are downregulated. So potentially, opioids may not be that good for neuropathic pain, and certainly the evidence from the clinical studies is that the number needed to treat is quite high. You need a really careful analysis and discussion, on a case-by-case basis. If you have patients who are really struggling, and opioids work for them, that’s fine. But my feeling from having worked with opioids over many years is that sometimes patients with neuropathic pain who run into problems get partial benefit, and then they develop a bit of tolerance and the benefit wears off, and they end up with an ever-increasing dose, resulting in physical dependence, withdrawal, and sometimes addiction.
What are the most challenging aspects of your research, and why?
Where to start? I enjoy the challenges of research; otherwise, I wouldn’t be doing it. You have to be very optimistic to do research, and for me it’s a balance between having a busy clinical practice and finding time to do all the research there is to do. One of the challenges for me is that there are so many research questions that are all very interesting, and so it’s about focusing on the ones that you can realistically work on in the number of days in a week that you have.
What are the key research questions in neuropathic pain that need to be addressed?
In terms of CIPN, one of the key things is, how do we assess it? We have very good guidelines for assessing neuropathic pain in general, and these are currently being updated, but CIPN is unique because you’re not only looking at the disease process of neuropathic pain, but also the coexisting, underlying diagnosis of cancer, and in addition to that there is the toxic insult of chemotherapy.
There’s no international consensus as to exactly how you make the diagnosis of CIPN, whereas for neuropathic pain in general you have gradings of definite, probable, or possible neuropathic pain. And in terms of assessment, when we’re looking at the published literature, some of the older studies used the CTC [common toxicity criteria] for adverse effects, which is routinely used in clinical practice, but while it grades neuropathy, it doesn’t look at pain at all, so we need to develop a proper way of assessing CIPN.
Another key challenge with CIPN is how to prevent it, but this is also an absolutely ideal opportunity for that because it’s a predictable and timed toxic insult. So it’s about understanding the mechanisms of CIPN and targeting those so that in the future we can prevent it, rather than struggle to manage patients with really debilitating neuropathic pain who are referred to the pain clinic several years after they’re finished with chemotherapy.
What advice do you have for early-career investigators?
As a researcher you have to love what you’re doing, so go for a research position in an area that you’re passionate about. You have to do that because it takes up so much of your life, and then you’ll have a job that’s hugely enjoyable and rewarding.
What do you do for fun when you are not doing science—any hobbies?
My main hobby, and that of my children, is horse riding. My girls like eventing, which includes dressage, show jumping, and cross-country riding; watching that as a parent can be slightly stressful at times. So I don’t have a lot of time to sit around at home because we have four horses, and we’re in the process of buying another one. I’ve had to learn how to drive a large truck; I’ve got my heavy goods vehicle license and I’m licensed to drive a truck up to 38 tons. Most of my weekends are spent driving around the countryside going to various competitions.
Brenda Dyal, PhD, DNP, is a postdoctoral associate at the University of Florida, Gainesville, US.