BREAKTHROUGH: Did you always want to be a doctor?
DR. BERDE: No. It was an idea that came to mind sometime during high school, but not
with any certainty. At times during high school, I thought I could be anything from a
basic researcher to a school teacher to a journalist to a lot of different things. The
ideas that health sciences were interesting, that biological sciences combined with
working with people sort of crystallized during college as a way of combining different
interests. I like working with people, I like biology and biological sciences, and as a
professional role, I like medicine in terms of the kind of relationships you have with
patients, the ability to do something useful for patients, and the kind of connection to
people you can have with that.
I think there are a lot of other interesting professions out there. My father was a
lawyer, retired from that a couple of years ago. There are interesting things about that,
but it is a very adversarial thing. Somehow the idea that most of the time you are working
with the patient on a common goal of getting them better struck me as more fun than the
adversarial system of the legal profession. Early on in college, it became clear to me
that medicine was the right way of combining my interests.
BREAKTHROUGH: When did you pick your specialty?
DR. BERDE: It was in medical school. In the last half of medical school, you do
rotations through different clinical specialties, and I got very interested in Pediatrics
and Intensive Care and Anesthesiology as a way of combining various interests, so I knew
by the end of medical school that I was going to do a combined residency, doing Pediatrics
and Anesthesiology. For a great many people doing Intensive Care in Pediatrics, that's the
route to go.
When I was finishing medical school, I made arrangements - I was at Stanford then - and
I came here to Boston to do residency here at Children's in Pediatrics and do residency in
Anesthesiology at Mass General across town. That training was initially intended to do
Intensive Care as my main specialty, and Pediatric Anesthesiology.
I still do a little bit of Intensive Care. I cover on weekends as one of the backup
covering people. I love doing that - it's a lot of fun. Because it's a very exciting and
immediate kind of medicine, the kind of medicine where the things you do matter a lot to
people. I like taking care of people who are very sick and you have some potential to make
them better. I like taking care of acutely ill people. It's exciting. You don't make
everybody better, but you make some people better and you can make other people
comfortable. You do what you can for a lot of people. So, I like it very much.
I knew from about halfway into medical school that I wanted to work with children, and
so I gravitated toward Pediatrics and, as I mentioned, Pediatric Intensive Care and
Pediatric Anesthesiology as a way of combining my interests. I was drawn to Acute Care
Pediatrics, ICU as a very exciting subspecialty, something that was a use of all the
physiology and pharmacology that one learns and where there's a potential to do good for
people. It was exciting, it was something that I gravitated toward.
So, training with combined residencies in Pediatrics and Anesthesiology was a pathway
towards doing Pediatric Intensive Care. I started out doing that most of my time when I
came on staff here in 1985 and I still do a very little of it. I cover in the ICU on
weekends about 1 weekend every 3 or 4 months. It's exciting and fun, and it's a place I
worked for a long time and feel a very close connection to that ICU.
In my first year on staff here, I got interested in what was a research area that was
not being explored in Pediatrics. Also, as I was doing Intensive Care in Anesthesiology,
it became clear to me there was a role for people to do pain management in children as a
subspecialty in its own right. In adult medicine, since about the late 1940's/early
1950's, largely through the work of John Bonika and others, there was a realization that
multidisciplinary approaches to chronic pain are useful.
Taking care of people with chronic pain requires the expertise of many different kinds
of physicians, psychologists, physical therapists, nurses, a broad range of health
providers. It can't be approached as a purely medical problem or purely psychological or
psychiatric problem, but it requires a broad-based approach. Bonika's development of a
multidisciplinary clinic in Seattle, in very close collaboration with psychologists such
as Wilbert Fordeis, really set a model for adult pain management back as early as the
1950's. In adults, there was also the development of acute pain services. The notion that
postoperative pain could be managed better by dedicated specialists who are concerned with
optimizing pharmacological management of postoperative pain is an idea that arose in the
70's and early 80's.
When I came on staff here in '85, I got interested in that, and during my residency in
Anesthesiology I spent a little time working with the adult pain specialist at Mass
General who was there at the time, observing a little bit of what he did. I got interested
in that. On occasion, I would be called by colleagues of mine and asked 'what would you do
for this kid with cancer who has unrelieved pain.' or 'what would you do for this kid with
cystic fibrosis who has unrelieved pain?' Very informally, I started doing pain
consultation, just on a case-by-case basis. When it became clear to the people around me
that I had an interest in that, suddenly I was being sent patients all over the place who
had difficult-to-manage problems.
This Children's Hospital serves infants and newborns and kids of all ages, but also a
considerable number of young adults. As you saw today in the clinic, we see a lot of
people who had a childhood critical illness, childhood cancer, and continue to come here
for long- term care even though they're in their 20's There are people with congenital
heart disease who come here in their 20's and 30's.
There are a lot of illnesses where kids were told growing up 'you're not going to live
beyond 20,' cystic fibrosis being an example where, back when I was an intern the median
survival was about 19. There is this whole generation of young adults with cystic fibrosis
who were told 'you will probably live until you're 20,' and they're now finding themselves
25, 30, 35 years old doing rather well, many of them doing rather well. Many of them are
chronically ill, many of them have a lot of medical problems, but there is this whole
cohort of young adults who continue to come to Children's Hospital because that's where
the expertise of extending the lifespan of people with these chronic illnesses has been
fostered. It's a long-winded way of saying that we end up in our clinic taking care of a
fair number of young adults with chronic illness that started in childhood.
BREAKTHROUGH: Why do you want to help children?
DR. BERDE: One of the best things we can do in medicine is to relieve pain -in people
of any age. It is a very fortunate occasion when we are able to make people more
comfortable. It's one of the most fun parts of medicine. There is a part of medicine that
involves fixing things that are wrong, much like an auto mechanic fixes cars. There is a
part of medicine that involves comforting people and relieving their symptoms, and I think
that is very rewarding. It's very rewarding to have somebody go from being in severe pain
to having no pain. Relieving their pain is something I like to do.
BREAKTHROUGH: What kinds of pain are you talking about?
DR. BERDE: There is no doubt that having the experience of pain is very important to
all of us. In fact, pain protects us from harm. If you don't feel pain, and you put your
hand on a burning stove and you don't feel it burning your skin, you will injure your
hand. There are a number of diseases in which patients don't feel pain properly, and that
causes problems for them. The most common example is people who have sustained spinal cord
injury with resulting paraplegia. Because they cannot feel parts of their body, they can
get skin ulcers - skin breakdown in areas where they are numb. So, pain protects us from
potential injury. It alerts patients to go to a physician and alerts physicians to try and
figure out what is wrong, what is causing the pain. That is protective pain: pain that
signals when something is wrong.
There are kinds of pain which signal that something is wrong and it's very clear what
should be done about it. If somebody has appendicitis, they don't just need pain-relieving
medicines. They need to go into an operating room and have a general surgeon take out
their appendix. After surgery they will experience a new kind of pain due to the operative
incision. This pain will last for a little while, a period of days - but the way you treat
the pain of appendicitis is by removing the inflamed appendix. Specific treatment of
specific disease is one of the ways all branches of medicine treat pain. Indeed, all
branches of medicine treat pain.
There are aspects of pain which are not protective, and which don't keep us from harm,
but they are readily treatable. Most pain after surgery is due to cutting through tissue,
and that pain does not protect you from harm. However, there are some kinds of pain after
surgery that signal to the surgeon that something is going wrong. If a cast is too tight
after an orthopedic operation, pain may be a signal that the cast is too tight and that
the cast needs to be split. If you have pain in an unexpected place, that can be a signal
that there is some other problem - a lung collapse, for example.
Most pain due to operative incisions does not protect us from harm, and relieving that
pain can help patients recover faster, get out of bed earlier, eat sooner and be more
active - that sort of thing. A lot of the aim in treating postoperative pain is to make
people more comfortable and to alleviate suffering. But the aim is also to do this with a
minimum of sleepiness, nausea and delayed eating. A lot of our research in treating
post-operative pain involves proper balancing of pain relief against the side effects of
medication.
After general anesthesia, a certain percentage of people will feel nauseated. There are
medications which diminish the risk of nausea. A lot of what we study are methods of pain
relief that cause less nausea, less sleepiness and less depression of people's breathing,
and that prevent a range of other post-operative complications.
BREAKTHROUGH: Is children's pain more difficult to manage and diagnose?
DR. BERDE: In some respects, yes. Particularly in infants and children that are too
young to speak to you. The main way we discover our patients are hurting is by asking
them. An articulate older patient, who speaks your language, with whom you can talk, tells
you a lot by conversing with you. The main way that physicians come to know what is going
on with their patients is by asking them questions. A one-year-old cannot tell you what is
going on with them, so our methods of finding out what is bothering them and where they
hurt are much more indirect and much more secondary. It is much more difficult to measure
or assess pain in the young infant.
Most of the pharmacology of pain medications is reasonably similar in comparison of
older children to adults. Some of the differences are in the very youngest of infants.
Newborns in particular may metabolize certain drugs differently, and it may be a little
more difficult to titrate or adjust doses of their medications. There is a whole science
around children's pain. There are whole clinical subspecialties around managing pain after
surgery, managing pain with cancer, and pain with nerve injuries. There are groups of
people at a few centers around the country and around the world who specialize in handling
difficult-to-manage problems due to pain in children. For example, dealing with kids that
have a nerve injury that stays painful for a long period of time or kids who have cancer
that is painful. These groups are discovering the best ways of handling pain after
surgery.
BREAKTHROUGH: What are we learning from all this?
DR. BERDE: We are learning that infants feel pain. That seems like something everybody
ought to know, but I think the medical community is becoming more convinced of it. We are
learning that very young infants, even newborns, have a neurologic apparatus to feel pain.
We're learning that untreated pain has adverse consequences. We are learning that pain
medications can be used in most situations with a very good margin of safety.
If you're a child with cancer or if you're a child having surgery, you can take opioid
analgesics - narcotic medicines - with a very good margin of safety. They cause a fair
number of mild and annoying side effects, and they are not trivial to use, but they can be
used effectively and safely in most situations. We have learned a lot more about
age-related differences in how children manifest pain. We have learned how to better tell
when a 2-year old or a 6-month old is feeling pain, as opposed to fear, as opposed to some
other symptom. We are learning, in newborns, better ways of measuring pain-related
behaviors. There is a lot of basic research on the development of pain mechanisms and the
neurologic differences in the very young infant, in terms of their pain responses.
I think medicine in general has had an inordinate concern with the risks of opioid
analgesics. There are very real reasons for society to be concerned about the misuse of
narcotics - of opioid analgesics. Certainly drug abuse is a serious social problem.
Another problem is that drug abuse has been confused with proper use of opioid analgesics.
There are very proper medical uses of opioids for managing pain after surgery, for
managing pain with cancer and for managing chronic pain due to a number of other
illnesses. In our concern for drug diversion and drug abuse, many times there is excessive
restriction placed on the use of narcotic medications - opioid medications - for patients
with pain. That applies to adults and children.
In much of the world, if you were a physician treating a patient with cancer and you
wanted to give them morphine for use at home, there would be government restrictions
against doing that because of government confusion between the proper use of opioids for
treating pain and the improper use of them for drug abuse. So, I think for both children
and adults, we have a lot more to change in terms of attitudes about using opioid
medications.
Another area that needs a great deal of improvement is the optimization of pain relief
and minimization of side effects. Opioid analgesics are useful and they relieve a lot of
pain, but they cause a fair number of side effects, such as sleepiness, nausea, dizziness,
inability to urinate, constipation... a whole range of symptoms. Finding better ways of
diminishing those side effects is important.
The most common pain medications used in the United States are nonsteroidal
anti-inflammatory drugs such as ibuprofen and naprosin...and medications like
acetaminophen (Tylenol). They are useful but they have some limitations. They have a
"ceiling effect" on their pain relief, meaning that if you give 3 grams of
aspirin or 3 grams of acetaminophen to a patient, you don't get more relief in an adult
than you would from 1 1/2 or 2 grams. The relief maxes out at a certain level. Related
problems are the side effects, so that in people taking anti-inflammatories for arthritis,
for example, a fair number of people cannot tolerate them due to stomach irritation,
stomach bleeding, or the effects on their kidneys.
There is new research taking place on ways of separating the
pain-relieving and anti-inflammatory effects (the good effects) of those types of drugs
from their stomach-irritating or stomach bleeding effects (the negative effects). I think
there will be an exciting series of developments in research, and we will discover that
some of these new drugs will have the beneficial effects without some of those risks and
side effects.
BREAKTHROUGH: What about the research into drugs
that work in terms of weeks instead of hours?
DR. BERDE: You are all familiar with local anesthetics. When people talk about local
anesthetics, they often use the term Novocain, although the most commonly used local
anesthetic, if you go to the dentist, is lidocaine. Local anesthetics do several things:
they numb a part of the body, they relieve pain, and they may make muscles weak. In some
situations it is useful to have a local anesthetic wear off very quickly. After you go to
the dentist for a filling, and you get home and find yourself biting the inside of your
cheek and drooling out the side of your mouth, you wish it would wear off quickly.
But there are many situations where if you had a local anesthetic during surgery that
wouldn't wear off for a week, it would be extremely useful. For example, let's say you are
having a chest operation and your chest needs to be split open. If the surgeon could numb
under five ribs while the chest is open and the numbness would relieve the pain from
coughing after a chest operation for five to seven days, that would be extremely useful.
It would provide the kind of pain relief that makes you less sleepy, with less of the side
effects of opioids. So, for about the last six years, my laboratory has been working on
developing several types of local anesthetics that last for several days at a time. We are
creating medications that would last for two days, five days, seven days or ten days.
One of the great things about major biomedical research institutions is that there are
a lot of people who have ideas for new inventions. At many institutions like Children's
Hospital, there is a whole office involved in taking inventions and linking people up to
research and development companies, or pharmaceutical companies that can take the
inventions into clinical use. We have done this at Children's Hospital in Boston with the
Technology Transfer Program. Working with the technology office here at Children's, under
the direction of John Lombardi, we have had licensure and research contracts with
pharmaceutical companies for developing some of these medications.
Our first generation of new local anesthetics that last for many days are now in early
human trials. They started first in the research and development phase, and now they are
being tested in what are called Phase I clinical trials. These trials are currently taking
place in other countries, but we hope they will be coming to the United States as early as
this winter. Again, the idea behind the new local anesthetics is to numb parts of the body
where being numb is not a problem. In other words, if part of your chest wall or part of
your belly is numb after surgery, or if you're numb in the area of a hernia operation, you
don't lose any protective sensation. You would not want to have your arm numb after an arm
operation for a week, because in most cases you need to be able to use your arm and move
it around. But having areas of your chest and belly numb and ensuring that you are
comfortable but not very sleepy or nauseated, and that you aren't having side effects from
other types of pain medications, that would be very useful.
BREAKTHROUGH: Is this a good area to be in right now?
DR. BERDE: I think so. I think pain management is an area where there is a lot of basic
neurobiology being applied to discovering better methods of treatment. I think in research
labs and in academic centers like the National Institutes of Health, and at major
pharmaceutical companies, there is an enormous explosion of research on how to take some
of the new neurobiology research and some of the new molecular biology research and use it
to make better pain medicines. Making pain medicine that is safer, has less side effects
and works for different kinds of pain.
Most of what we have talked about so far is pain due to injury of tissues: pain after
surgery, pain from arthritis - things like that. There is a whole different type of
persistent pain that we see in a lot of patients here in the clinic. Some of the patients
you met today have pain like this. This type of pain is called neuropathic pain, or nerve
pain. Ordinary pain, or what we call nociceptive pain, involves largely intact nerves that
are detecting that some part of the body is either inflamed or injured.
The other kind of pain, nerve pain, involves injury to major nerves themselves or
inflammation of the nerves or degeneration of the nerves, and involves abnormal
excitability, abnormal firing patterns in the nerves themselves. That is what we call
neuropathic pain. Neuropathic pain is reasonably common. People with diabetes feel a pain
as if their feet are on fire. People who have had shingles often feel a shooting,
stabbing, burning pain on an area of their chest wall. Amputees often feel pain after an
amputation where their missing foot feels painful. In that case, pain is being referred to
a part of the body that is not there any more.
Those are all examples of neuropathic pain. One of the things that has become clear is
that different types of medication help neuropathic pain. Medicines that were originally
developed to treat depression or even epilepsy sometimes can help people with nerve pain.
BREAKTHROUGH: Is there any hope for those patients with neuropathic pain?
DR. BERDE: Neuropathic pain problems certainly are difficult to handle, but I think
there is reason for hope. A certain percentage of people with neuropathic pain can get
pain relief from the medications we talked about earlier: antidepressants and epilepsy
medications certainly help a number of them. For many people, the medications can help,
but at a price of severe side effects. There are many people who can get pain relief from
an antidepressant medication, but it makes them sleepy or they have blurry vision or they
have dry mouth or experience dizziness. This is particularly a problem in the elderly
because many of them have neuropathic pain, and for many of them the amount of Elavil or
amitriptyline that relieves their pain also makes them dizzy or sleepy.
I think neuropathic pain problems are difficult and they are challenging, but there is
still hope for treatment in many cases. There isn't a road map to tell which patient will
get better with an antidepressant medicine or with an epilepsy medicine, or some other
type of medicine. There is a lot of trial and error involved.
It used to be said that nerve pain or neuropathic pain does not respond to opioid
analgesics. It is true that if you look at a large number of people with neuropathic pain,
a considerable percentage of them only get relief from opioids at doses that put them to
sleep. It makes them sleepy all the time. But there is a subgroup of people with
neuropathic pain that get reasonable pain relief at doses of opioids that allow them to
function, to be pretty clear-headed, and to live reasonable lives.
You saw that today with my patient Richard Evans. Mr. Evans, as you know, had a serious
form of cancer, and a number of surgeries to extract the cancer. In order to get the
cancer out and save his life, it was necessary to cut across nerves in his body and it was
necessary to put prosthetic materials into his leg. This has resulted in large areas of
pain in his leg due to nerve regeneration and nerve injury. A number of medications have
been administered to him over the years. It has turned out that opioid analgesics give him
pain relief which allows him to work, run a business, drive, think clearly, have a sense
of humor and to make business calculations in a clear-headed way. He has quality of life
in addition to pain relief.
However, for many people with neuropathic pain, you can't find an amount of opioid that
will make them comfortable without making them too sleepy, too dizzy or too confused.
There is enormous individual variation for pain treatment and pain management. We end up
making a lot of individual adjustments. We must adjust the choice of medications to the
individual patient's overall situation. We must take lifestyle intervention and
psychological approaches to pain management, such as relaxation training, imagery and
self-hypnosis. There are many physical methods of pain management, such as transcutaneous
nerve stimulation, acupuncture and things like that, that could help some people. A lot of
it involves trial and error and seeing what works for that individual person. We have a
need for better road maps so we know early on what will work for each individual patient.
When someone like Robert White, whom you saw today, comes in, we need a better way of
choosing from the start what kinds of treatments will help him, rather than spending a
great deal of time in trial and error.
There is also hope for people with neuropathic pain based on new understanding of the
basic neurobiological mechanisms of abnormal nerve excitability. A lot of research on what
makes injured nerves hyperexcitable and what makes regenerating nerves cry out with pain
signals is helping us target medications and pain treatments in more effective ways than
we have now. So, I think this is an area where there will be a lot of new developments. I
think there is hope that patients will have better neuropathic pain treatment options in
the next ten to twenty years than they have now.
BREAKTHROUGH: Are you embarrassed by being named one of the Heroes of Medicine?
DR. BERDE: It isn't par for the course. I don't see myself as being unusual among
physicians. I work with a whole group of people here at Children's Hospital and I have
colleagues around the world who practice in ways very similar to my own. I have a lot of
my own heroes around here. There are people who work in this hospital whom I have regarded
as heroes of my own for years. I think I have had the good fortune to stumble into an area
where there was something important to do. I came into the field of pain management at a
time when very few people were working with pain in children. I also had the good fortune
of being here at Children's Hospital, where there was a whole group of people in different
specialties who have similar interests. A lot of my job was simply pulling these people in
different specialties together.
Let me give you some examples of that. There is a psychologist whom you met today,
Bruce Masek, who has for seventeen years now, looked at psychological methods of pain
management. He has studied ways of using the mind to tune out, tune down, or diminish
pain. It isn't voodoo or mysterious or anything, they are just ways of guiding attention,
of putting the body in a relaxed state. They are methods of teaching people how to better
cope with pain, and how to make lifestyle adjustments that will allow them to manage their
chronic illness more effectively. He has performed a number of systematic studies looking
at how children manage headaches with these techniques. He looks at what components of the
regimen are most essential, and how you can teach children to manage their headaches in a
way that is efficient and that has long-lasting results.
When I started collecting colleagues to do pain management, there were people like
Bruce Masek to collaborate with. There was a group of nurses here that was very interested
in improving care in the postoperative wards and the cancer wards. This collaboration was
very useful.
A whole range of physicians in the hospital have had similar interests. For example,
one of the orthopedic surgeons, Lyle McHaley, is a renowned sports medicine specialist. He
cares for the Boston Ballet and other dancers throughout New England. He cares for
gymnasts and athletes of all sorts, and has developed both a great expertise in managing
orthopedic problems and a very broad-based, sophisticated sense of how to help people who
have chronic musculoskeletal injuries and pain. There was a ready collaboration with him,
with several rheumatologists, oncologists, orthopedic surgeons, neurosurgeons,
neurologists... a whole range of specialists. Part of my good fortune has been working at
a place like Children's. It is a truly unique place.
BREAKTHROUGH: How much longer can you keep this up?
DR. BERDE: I think I can keep it up. I am very fortunate to have colleagues with whom I
share the work. I have friends around the U.S. where they are the only person doing pain
management at their hospital. They have a harder job than I do. I have partners like Bob
Wilder and Neville Sephna to share a lot of the work with. I have colleagues like Karen
Van Curan and Polly Skoptan who care for a lot of the ongoing clinical care. I have a very
fortunate position here, in large measure, because of the foresight and the backing of our
Department Chairman, Paul Hickey, who is the Chairman of the Department of Anesthesia. He
has taken a very proactive role in backing our program, and in helping me get the
resources to make it work. I think I probably have it easier than a lot of people running
pain programs around the country.
I probably work less now than I did ten years ago. I work shorter hours. I don't see
myself changing my area of interest or my focus. I'm in a position where many people think
about becoming a Department Chairman, but I am not sure that is something I want to do at
this point. I think doing the work I am doing, both the laboratory research and the
clinical research, and the work I do in clinical care seems more exciting and more
interesting to me, at this point, than running a department.
BREAKTHROUGH: How important is the support of your family?
DR. BERDE: It is very important, in several ways. I think taking care of people with
critical illness and taking care of people with chronic illness is hard and at times
frustrating. I think it would be very hard to do this without having a very strong family
connection, a wonderful loving family to support my doing this kind of work.
I think my inclination to do this kind of work was supported by my wife, who has a
unique perspective on chronic illness and the emotional care of children. My wife is an
artist. For eleven years she worked at Children's as an art therapist and child life
specialist on the adolescent medical ward. She did a lot of work with kids with terminal
illnesses, kids with cystic fibrosis and other life-threatening illnesses. She has a
spectacular perspective on what people with chronic illness are going through and on the
role of attitudinal factors, the role of hope and support and emotional factors in dealing
with their illness. She used a variety of approaches, art being one of them because that
was where her training was. By using art therapy and by just providing patients with
support and somebody to talk to, she helped them find ways of coping with their illness.
We didn't talk much about it early on, but I think her example in how she cared for kids
as an art therapist was a strong force in moving me toward pain management and pain
treatment as a career.
BREAKTHROUGH: Does she still do that kind of work?
DR. BERDE: She is now an artist in residence in the Brookline schools, and she gives
lectures on art therapy at colleges in the Boston area. She still keeps in touch with a
number of the kids she cared for over the years, many of whom are now in their thirties
and forties.
BREAKTHROUGH: Thank you, Dr. Berde.
DR. BERDE: You're welcome.
