DREAM CAMPAIGN SUPPORTS 11 RESEARCH FUNDING PRIORITIES
Duke Dream Campaign Podcast
Genomics of Pain
Andy Shaw, MD
Hello I’m Elizabeth Perez and welcome to the Duke Dream Campaign Podcast.
We are here with anesthesiologist and researcher, Dr. Andy Shaw who is best known for his revolutionary work with iPEGASUS, a study that collaborates data from institutions around the world. Dr. Shaw’s research interests center around the genetics of perioperative medicine, particularly the role of genetic variation in the response to cardiothoracic surgery, and in postoperative acute renal failure. Three of his research endeavors, including iPEGASUS are part of the 11 funding priorities of the Duke DREAM Campaign. Today we will be discussing his study, Genomics of Pain. Dr. Shaw, thank you for taking the time to talk with us today.
Briefly describe this study.
This is a study titled the Genomics of Pain. The point behind the study is to try and understand the aspects of individual patients’ genetic make-up that will allow us to try and predict how they will respond to a surgical intervention or an operation, particularly in terms of pain and quality of life.
Most people think of their anesthesiologists as the person who will put them to sleep during surgery. And if they are asleep they wont feel pain. Can you explain the anesthesiologist’s role especially as it relates to dealing with pain and how the care their receive in the operating room can impact their quality of life?
Anesthesiologists look after a patient before, during and after their operation and also in the intensive care unit and the chronic pain clinic. One of our jobs is to make sure that before, during and after surgery, patients are not experiencing unrealistic amounts of pain. While we do put people to sleep for their operation, we also take care of them while they are asleep. Part of that care is minimizing the amount of pain that someone perceives.
When people are asleep they do not actually feel pain, they perceive “No Susception”, which is a noxious stimulus. People respond to noxious stimuli in different ways. Part of the skill of an anesthesiologist is to recognize when a patient who is not able to communicate in conventional form, is experiencing something unpleasant, also known as pain. Anesthesiologists are trained to recognize pain, recognize the things that cause pain and to deal with them preventatively and also in a rescue fashion.
For example in the post anesthesia care unit, we may use different types of drugs, anesthetics, a regional anesthetic, and or use a combination of all of these things in order to try and reduce the side effects of each of these techniques but maximize the benefits that each patient receives.
If patients do not actually feel pain while they are asleep but they feel a noxious stimulus how does that differ from pain? And if a patient wakes up during surgery does that mean that the patient will feel pain?
Everyone is worried about waking up when they are supposed to be asleep. It is important to differentiate between the times when we want the patient to wake up and the times that we do not. It may be a little strange to expect someone to wake up during an operation but there are operations when it is very important to wake someone up during the procedure.
For example, during a surgery on the spinal cord, the patient is woken up to make sure they can move their feet. There is a technique called a “deliberate wake up” in which we actually wake patients up during an operation to make sure that everything is okay from a neurological perspective. There are strong painkillers available that will allow us to do that so that the patient will not feel pain at the time that they wake up. Most people are afraid about experiencing what is called awareness under anesthesia and this is currently a very hot topic.
The overall incidents of awareness is thought to be somewhere between 1 in 1000 and 1 in 500 patients, but that does not really tell the whole story because almost all cases of awareness occur in very high risk patients; people that are either extremely sick or have been involved in a major accident. There is a danger in giving them the amount of anesthetic it would take to put them completely to sleep because it may also end up killing them. There is a very fine balance between giving someone enough anesthetic that they are comfortable for their procedure and do not remember, but not so much that you actually endanger their life.
It is important to get the risk of awareness in perspective with the risk of other things that also happen in the perioperative period. For example, wound infections or chest infections are both many times more likely to occur than awareness and are also likely to threaten someone’s health. This however, people view this as almost an acceptable risk of the operation.
Many people may not realize that their anesthesiologist is managing the whole patient, like keeping them alive and preventing life treating events beyond just putting them to sleep. I heard that recently pain has been called the fifth vital sign; why is that?
Traditionally in medicine we have four vital signs; pulse, blood pressure, respiratory rate and temperature. In an effort to improve physicians’ and nurses’ understanding of pain as a problem, we introduced the fifth vital sign, pain. We record pain on what we call a visual analog scale or a numerical scale. We say to people that 0 is no pain and ten is the worst pain imaginable and we ask them to give us a number and we chart that every time we see them on round. We record that information along with the other 4 vital signs in the clinic every time someone comes to see us.
Isn’t pain subjective? How can you objectively measure pain especially during surgery, when a patient is asleep and won’t be able to tell you?
It is very easy for someone to say “ouch” if they are awake, but of course it is much harder for us to recognize if someone is feeling a noxious stimulus or pain while they are asleep so we have to look to other ways to detect that. Typically, the signs that someone is experiencing discomfort while asleep are; increase in heart rate, increase in blood pressure, and sometimes people will sweat slightly while asleep. These are the sorts of things we look for particularly if they respond to the administration of a strong narcotic which is what we would usually do while someone is asleep.
Using the temperature of which somebody feels a metal plate is hot or cold, or the time it takes to perceive that the plate is hot or cold are examples of the ways to quantify the different types of pain such as thermal pain, burning pain and etc.
Let’s talk about chronic pain. In the year 2000 it was estimated that 75 million Americans suffered from chronic pain. Can you tell us the difference between chronic and acute pain and what causes these different types of pain?
Let us take the example of a patient who comes to have a lung cancer resected. These patients undergo a procedure called a thoracotomy, which is when the surgeon opens the chest and removes the part of the lung that contains the lung cancer. In the immediate period after the operation, for about the first week or so, the type of pain that people feel is what we call an acute, somatic, sharp, stabbing-type pain. Everybody is familiar with that; it is the pain you have when you cut yourself. As you can imagine, the deeper you cut, the more it hurts. That is what acute pain is and almost everybody is familiar with acute pain.
However, in about 30-50% of patients, that acute pain will give way to a different type of burning, what we call a neuropathic, disasthetic pain, which is described by patients as a dragging, burning sensation. That can persist into some patients for years after their surgery, and is extremely distressing. Unfortunately this type of pain is extremely difficult to treat.
The difference between acute and chronic pain is really a temporal one. While an acute pain occurs early after an initiating event like an operation, chronic pain occurs later in the course. But chronic pain is not only much harder to treat but much more persistent as well. For these reasons, the chronic pain condition is miserable and that is what this study is designed to address.
Have there been any studies that look at why chronic pain exists in certain patients? And is this something that may also be linked to genetics? Are you suggesting that some patients may experience more pain because of their genes?
Absolutely, that is what we are suggesting. Everybody is familiar with the concept of higher or lower threshold of pain. You will hear people say, “Oh I don’t tolerate pain well,” or “I have a very high pain threshold.” They are describing the way that they perceive the same stimulus that someone else experiences, but at a higher or lower threshold. What people are saying when they describe their own pain threshold is their own genetic predisposition to perceive a given stimulus as painful. Our goal is to try and tap into that by measuring the different types of genes that different people have and seeing if there are patterns between them. We would potentially do things differently before, during and after surgery if we knew who was more or less likely to experience both a severe type of acute pain and perhaps more importantly, who was likely to go on and develop a chronic pain syndrome.
I thought that our genes were something we were born with and couldn’t change. Even if there is a link between our genes and the way we experience pain, how does this affect a patient’s care?
Let us fast-forward perhaps 5 years, to the point where you might be coming up for an operation. First you would come to see us in the preoperative clinic. We would either take a skin smear from inside your cheek or perhaps a drop of blood. We would look at the genetic makeup in your cells and from that information we could determine whether you were at a low, intermediate or high risk for developing a particular type of pain syndrome. We could then treat you differently according to the results of that test. One of the other things we could do is since we know different people handle different drugs in different ways, we would give people different drugs depending on the way they are likely to respond. At the moment, it is almost entirely random how people respond to treatment because we do not tend to individualize therapy as we, in our group, believe we should.
Our work tries to tap into the individualization of each patient’s treatment so we can tailor our care specifically to the treatments that we know they will benefit from the most and of course the treatments that we know from which they will suffer the least side effects.
Thank you for listening to the Duke Dream Campaign podcast. Special thanks Tom Freeland and to our producer, Cindy Cho. For more information about this research project or how you help this featured research project come through fruition, please visit us at http://dreamcampaign.duhs.duke.edu or call (919) 681-2849.
To learn more about our 11 funding priorities please click on the images above.
If you are interested in becoming a donor to the Duke Dream Campaign, please contact Elizabeth Perez at 919-681-2849.