Understanding the Genetics of Pain: A Conversation With Luda Diatchenko

Luda DiatchenkoEditor’s Note: The first-ever North American Pain School (NAPS) took place from June 26-30, 2016 in Montebello, Quebec, Canada. This educational initiative brought together leading experts in pain research and management to provide 30 trainees–part of the up-and-coming generation of pain researchers–with scientific education, professional development and networking experiences. Six of the trainees were also selected to provide first-hand reporting from the event, including interviews with visiting faculty members. An interview with pain genetics researcher Luda Diatchenko appears below. 

Luda Diatchenko, Ph.D., is Canada Excellence Research Chair in Human Pain Genetics and Professor in the Departments of Anesthesia and Dentistry at the Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada. Her research focuses on how genetic variations impact human pain perception and the risk of developing chronic pain conditions, with the goal of discovering individualized treatments for pain. One project she is involved with is called OPPERA, which is examining the genetics of orofacial pain. Diatchenko sat down at NAPS with Ram Kandasamy, a fifth-year PhD candidate in neuroscience at Washington State University, Vancouver, US, to discuss OPPERA, other projects in her lab, and the challenges of pain research. Below is an edited transcript of their conversation. 

How did you become interested in pain research?

My original background is in molecular genetics. I first worked in industry, developing methods to investigate gene expression [the turning on or off of genes]. Then I worked in academia at the University of North Carolina at Chapel Hill, because I wanted to gain some university experience. One of my colleagues there, Bill Maixner, asked me to help do some molecular analysis in a group of people characterized for how they responded to painful stimuli. I thought it would take me a just a few days, but it took much longer, and so I became very interested in studying pain. What fascinated me about pain was that it was so understudied, and also that it is a huge unaddressed health problem. Pain has a physiological component, a psychological component, and almost a philosophical component as well—people even argue what pain is. For all of those reasons, pain was very exciting to study.

What is the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study that you have been involved with?

OPPERA is the biggest study ever of orofacial pain, and is looking specifically at pain from temporomandibular joint and muscle disorders (TMJD)—jaw pain. OPPERA is funded by the National Institute of Dental and Craniofacial Research (NIDCR), and is the most expensive study it has funded.

OPPERA studies chronic TMJD patients, and compares them to healthy “control” subjects without TMJD. The study started in 2006, and the first results were published in 2011. The study enrolled 3,400 people at baseline who were characterized for multiple observable characteristics, known as phenotypes, including their responses to quantitative sensory testing (which tests nerve function), psychological distress, cognition, and other traits. Altogether, there are more than 205 questionnaires that study subjects have completed. We then followed these people—so far we’ve studied them for 12 years—to see who developed TMJD. Then, we looked at their baseline characteristics to see which ones could predict whether a person would develop TMJD.

The OPPERA team has now published over 50 research articles. The findings cover many aspects of characteristics differentiating chronic pain cases from healthy controls, as well as risk factors for developing chronic pain. Among the strongest effects we have observed is that psychological distress plays a substantial role in the pathophysiology of chronic facial pain. We also see a substantial contribution of physical trauma and enhanced sensitivity to painful stimuli. The co-occurrence of different chronic pain conditions also became very evident. For example, only 15% of chronic TMJD patients do not report any other chronic pain. The main genetic findings are still on the way, but will appear very soon.

What are some other projects underway in your lab?

Right now, the biggest project is part of the Strategy for Patient-Oriented Research (SPOR). SPOR is funded by the Canadian Institutes of Health Research (CIHR), and many centers in Canada are part of it. We have received a pain patient engagement grant, which we will use to study the genetic characteristics of almost 10,000 people. For this work, we will rely on the Quebec Pain Registry, which is a very well-characterized registry that has a lot of information about patients with pain, including data about the drugs used to treat them. We are going to follow these patients over time and study whether there are certain molecular characteristics, such as genetic variations called single nucleotide polymorphisms (SNPs), which predict a positive response to a drug.

The SPOR study just started, and our goal is to finish it in five years. Most of the study should be done relatively quickly because study subjects are already in the registry. We send them a kit to collect their saliva, from which we purify their DNA, which we then use to do our genetic studies.

From your perspective, what are the biggest challenges are in pain research?

A lack of funding is the biggest challenge, especially compared to other areas of scientific research. The biggest issue is that most people think that pain is not the fundamental problem. That is, they think that a person has a disease and that pain is a consequence of that disease. As a result, they say that you only need to study and treat the disease, and if you do that, the pain will go away.

But there is increasing recognition in the field of pain research that chronic pain is a disease of the central nervous system that persists even when the initial injury or trauma is no longer present. This is something that is not often understood, and I think that’s why funding levels for pain research are very low. The more we change how people view chronic pain—that it can be considered a disease in and of itself—the more people will become interested in pain research, and more funding will follow.

What is different between doing pain research in the United States vs. Canada?

The biggest difference is that in the U.S. grants support your salary, but in Canada your salary is paid by your university. This is an important difference because while Canadian researchers still need to write grants, the grants are used to support your research, not your position. This removes stress from your daily life, although some people argue that it doesn’t keep you on your toes as much.

I also notice that my colleagues and I are able to find funding from a number of different organizations, so I feel there are a lot of resources in Canada. In fact, an analysis has been performed on the relative contribution to different research fields in different countries, and Canada is number one in pain research. There are many very bright people here, and the more they contribute, the more funding that is available, and then these people train others who are also very good and can bring in funding.

What is the most exciting thing about the future of pain research?

We have a chance to actually uncover the pathophysiology of chronic pain—and we have a chance to find a way to treat it. It is exciting that we have an opportunity to find an answer to the unresolved question of what causes chronic pain.

Thank you for speaking to RELIEF.

Thank you.