You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Chronic Pain: Overcoming Treatment Barriers for Effective Outcomes

  • Authors: Faculty: Michael J. Brennan, MD; Howard A. Heit, MD, FACP, FASAM
Start Activity

Target Audience and Goal Statement

This activity is designed for physicians, nurses and pharmacists who have an interest in enhancing their knowledge and understanding of chronic pain.

Upon completion of this activity, participants will be able to:

  1. Describe traditional and novel pharmacologic interventions for chronic pain.
  2. Identify appropriate role of the primary care physician and pain specialist in the management of pain patients.
  3. Identify and distinguish among addiction, tolerance, and physical dependence, as well as understand pseudoaddiction and how to manage each appropriately.
  4. Summarize regulatory issues impacting health care providers relative to prescribing opioids.


It is the policy of MediCom Worldwide, Inc. to ensure balance, independence, objectivity and scientific rigor in all its sponsored educational activities. All faculty participating in the sponsored activity are expected to disclose to the audiences any real or apparent conflict(s) of interest related to the content of their presentation(s).


  • Michael Brennan, MD

    Senior Attending Physician, Department of Medicine, Bridgeport Hospital, Bridgeport, Connecticut


    Disclosure: Honoraria related to formal advisory activities: Endo Pharmaceuticals, Purdue Pharma L.P., Janssen Pharmaceutica Products, L.P.; Honoraria related to the development of educational materials: Purdue Pharma L.P., Janssen Pharmaceutica; Honoraria related to speakers' bureau activities: Cephalon, Inc., Purdue Pharma L.P., Pfizer Inc., Janssen Pharmaceutica; Grant support related to research activities: Janssen Pharmaceutica.

    Dr. Brennan indicated that his presentation would include the discussion of oral transmucosal fentanyl citrate (OTFC) for the management of noncancer pain. OTFC is not approved by the FDA for this use in the United States. Dr. Brennan indicated that his presentation would not include the discussion of products that have not been approved by the FDA for any use in the United States.

  • Howard Heit, MD, FACP, FASAM

    Board Certified in Internal Medicine and Gastroenterology/Hepatology, Certified in Addiction Medicine and as a Medical Review Officer; Chronic Pain Specialist.


    Disclosure: Honoraria related to the development of educational materials: Purdue Pharma L.P., Cephalon, Inc.; Honoraria related to speakers' bureau activities: Purdue Pharma L.P., Abbott Laboratories, Endo Pharmaceuticals, Cephalon.

    Dr. Heit indicated that his presentation would include the discussion of oral transmucosal fentanyl citrate (OTFC) in acute or chronic noncancer pain. Oral transmucosal fentanyl citrate is not approved by the FDA for this use in the United States. Dr. Heit indicated that his presentation would not include the discussion of products that have not been approved by the FDA for any use in the United States.

Accreditation Statements

    For Physicians

  • MediCom Worldwide, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

    MediCom Worldwide, Inc. designates this educational activity for a maximum of 1.5 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

    Contact This Provider

    For Nurses

  • MediCom Worldwide, Inc., 101 Washington Street, Morrisville, PA 19067 is approved by the California Board of Registered Nursing, Provider Number CEP11380. MediCom designates this CNE activity for 1.5 contact hours. Program Number: 04-043-139

    Contact This Provider

    For Pharmacists

  • MediCom Worldwide, Inc. is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Its CE programs are developed in accordance with the "Criteria for Quality and Interpretive Guidelines" of the ACPE. This program is acceptable for 1.5 hours of Continuing Education Credit (0.15 CEU). Universal Program Number: 827-999-04-043-HO1

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

The credit that you receive is based on your user profile.


Chronic Pain: Overcoming Treatment Barriers for Effective Outcomes

Authors: Faculty: Michael J. Brennan, MD; Howard A. Heit, MD, FACP, FASAMFaculty and Disclosures


Management of Chronic Pain: Evolution and Revolution, Presented by Michael J. Brennan, MD

The Quandary of Chronic Pain

  • At a quick glance, the topic of my talk, "Management of Chronic Pain: Evolution and Revolution," may seem a little bit disconnected from the focus of this program. But multiple studies that have been done by organizations ranging from the American College of Geriatrics to the American Academy of Pain Medicine suggest that there is a single primary issue that stands as a barrier to the proper treatment of patients with intractable pain. That barrier happens to be us; we -- physicians -- are the face of the enemy. Physicians and clinicians throughout the healthcare spectrum continue to remain the number 1 reason why patients in pain don't receive adequate care. So what I want to do is not a "how-to" lecture; the concept of trying to teach people how to manage pain in a primary care setting in a 35-minute window is impossible. What I'd rather do is spend time reviewing several key evolutionary steps that we've taken in the last 25 years in our understanding of pain, its pharmacology, its physiology, and some of the things that pain does to people.

  • Management of Chronic Pain: Evolution and Revolution

    Slide 1.

    Management of Chronic Pain: Evolution and Revolution

    (Enlarge Slide)
  • My father practiced for 45 years in New York City. He was the first board-certified internist in Brooklyn. And he used to moan and groan, like most of us, at the notion of treating his patients with diabetes who were in pain, individuals with postherpetic neuralgia, or others.

    I happened upon a quote by Sir William Osler in his collection of lectures called "Aequanimitas," which was published in 1947. Just think about this: it's 4:00 in the afternoon on a Friday. You've got nice plans for the weekend, your family is at home waiting for you, and in comes Mrs. Smith. She is a 50-year-old female with fibromyalgia. Now what does that do to the start of your weekend? For many physicians, the response s like "this is the last thing I want to deal with." Well, Osler -- who's perhaps the most influential physician ever to hail from North America -- quipped, "When I see a rheumatoid [meaning a fibromyalgia patient] walk in the front door, my tendency is to walk out the back door." If such a magnanimous, brilliant physician could be flustered by pain patients, well, we shouldn't feel so bad ourselves. Perhaps there's more there than meets the eye.

  • Slide

    Slide 2.

    Care of the Patient With "Chronic Pain"

    (Enlarge Slide)
  • Why are we bothered by this population of patients? Well, it's because they're frustrating; they're difficult for a number of reasons. First, by the age of 50, some 90% of the population experiences severe pain. Probably 95% of that severe pain goes away -- maybe 99%. What is it about some patients where they get an insult to the system and pain becomes persistent? Why is it that a static lesion can go from being an area of discomfort to an entire limb being painful? What is it about the nervous system in some people that makes it more pliable or malleable, if you will, to insult and injury?

    Why is it that only our pain patients get so crazy? Certainly patients on dialysis have a stressful, terrible life, but why is it that when we measure emotional scores -- and I'll show you some of these later -- that patients in chronic pain seem to be so much more disturbed than the average patient with a chronic disease? It doesn't make sense. Consider patients with fibromyalgia. There is no overt lesion; there are no broken bones, there are no crushed nerves. Why are their lives so disrupted?

    How do we assess pain? We can't hold something over somebody that will tell us their pain score. How often have you had a person that you've seen in the emergency room (ER) who says, "Doc, my pain is a 10. Catch the game last night?" You know, when I have a 10, I'm rolling around on the floor, sweating, and my blood pressure is off the chart -- there's a disconnect between the person who says he or she has a pain score of 10 and what we think a person who has a pain score of 10 should look like. We do not have any system yet that is commercially or readily clinically available to assess pain. We're getting there; positron emission tomography (PET) scanning and functional magnetic resonance images (MRIs) show distinct patterns of activity in the nervous system in individuals with a variety of pain states, but they still do not tell us the severity of that pain.

    Mrs. Smith has fibromyalgia; you give her everything, including opioids, and nothing seems to work -- she still complains of bitter pain. So why don't typical pain patients respond to typical therapies? Dr. Heit will talk about addiction and regulation, but we know from surveys of clinicians that these 2 issues play paramount roles in patients in treatment for pain.

  • Why?

    Slide 3.


    (Enlarge Slide)
  • So let's talk a little bit about pain. An insult -- a broken bone or carpal tunnel injury -- can lead to pain. Well, what do you do when you are in pain? You stop using that limb, which leads to decreased mobility and reduces your functional status. As you start to not do the things you used to do, there can be a loss of self-esteem and self-efficacy. You start to limit yourself, and this vicious cycle goes on and on. Another way that I like to try and describe it to clinicians is this: as an infant, you are born as this groping little thing trying to find your feet, putting everything into your mouth, getting sensory awareness. You then grow up as a member of a family; you get integrated into that family; you learn that you are not the only entity that exists. You develop into a mature adult and hopefully you become a viable, contributing member of your community and society. We'll call that integration, if you will. What pain does is it literally disintegrates people; it pulls them first away from those things they enjoy doing because it hurts. Then it starts to pull them away from their families. They start to withdraw, and ultimately pain takes them away from themselves. It makes people become different entities. And if you've seen enough people with intractable pain -- be it neuropathic pain, fibromyalgia, or arthritis -- you can see this phenomenon over time. That's the bad news. The good news is that with proper care, you can reintegrate people, perhaps not to their same functional status, but back to where they belong.

  • Vicious Cycle of Uncontrolled Pain

    Slide 4.

    Vicious Cycle of Uncontrolled Pain

    (Enlarge Slide)
  • According to the American Medical Association standards of ethics and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), pain management really is the role of every clinician in the United States. Pain is the number 1 symptom with which people present to your office or clinical setting. We need to assess it. It's a difficult assessment, but there are tools available.

  • Pain Management

    Slide 5.

    Pain Management

    (Enlarge Slide)
  • I was a strong proponent of JCAHO's standards being placed in clinics, hospitals, and nursing homes. And the reason for that was simple: I was tired of seeing patients who were taking pain medicines, who then came into the hospital, had a surgical procedure, and had all their medicines discontinued. So I think the JCAHO standards mandating better healthcare by giving better pain care were an important stride forward.

  • Excerpts from JCAHO Standards

    Slide 6.

    Excerpts from JCAHO Standards

    (Enlarge Slide)

What Is Meaningful Pain Reduction?

  • Let's start with a really important question. What is meaningful pain reduction? On a daily basis, patients come in saying, "you've got to get me out of this pain; this is terrible." We have to ask ourselves, "can we get patients pain-free; can we make them pain-free without side effects, without toxicities, and at reasonable cost?" I can make anybody pain-free, but I would have to intubate them by giving them enough intravenous sedation and analgesics. That's not a functional way to be.

    If we're fortunate enough with chronic progressive disease to get patients pain-free for a while, can we keep them there? Can we keep them there despite obvious disease progression or concurrent disease states? Finally, can we keep people pain-free despite tolerance?

  • What Is Meaningful Pain Reduction?

    Slide 7.

    What Is Meaningful Pain Reduction?

    (Enlarge Slide)
  • This study was published in 2001 in Pain; it suggested that we don't have to shoot for a 0 pain score on the 0-10 scale to make our patients feel as if there are benefits. If we can get that visual analog scale down consistently between 20% and 30%, patients describe that as being meaningful. And if you can get a patient's pain score down by an average of 50% and keep it there, patients describe that as very meaningful. So, experienced chronic pain patients recognize that they're never going to be out of pain all the time, but if you can consistently reduce their pain, even if you don't get it to a 0, you can make these people feel much better.

  • What Is Meaningful Pain Reduction?

    Slide 8.

    What Is Meaningful Pain Reduction?

    (Enlarge Slide)
  • This is a schematic that was created by Loeser from the University of Washington. He built up the notion of where pain comes from; it comes from a peripheral nociceptor. What does the central nervous system (CNS) do to it and what impact does that have on a person's mental status? What does that create as far as pain behaviors go? It is important for you to know that there is no such thing as simple therapy for an individual who has been suffering from chronic pain. Treating an intractable pain patient is not writing out a prescription for an opioid or a nonsteroidal anti-inflammatory drug (NSAID) and saying: "See you in 3 months." If somebody's really disabled with pain, we need to take a holistic approach and try to bring multiple interventions to maximize that individual's quality of life.

  • Pain: A Conceptual Approach to Treatment

    Slide 9.

    Pain: A Conceptual Approach to Treatment

    (Enlarge Slide)
  • So evolution leads to revolution and in the last 25 years, there's been a tremendous improvement in our understanding of the physiology of pain, much of it done in Boston. Woolf at Harvard has done incredible work on elucidating molecular levels of pain. There has been tremendous improvement in the type of medicines that we can give our patients, along with a better understanding of addiction and abuse. These steps taken together have really been able to revolutionize the way we can treat our patients.

  • Evolution Leads to Revolution

    Slide 10.

    Evolution Leads to Revolution

    (Enlarge Slide)

First Evolutionary Step: Toward a Better Definition of Pain

  • What is pain? Pain has been defined by the International Association for the Study of Pain (IASP) in a committee consensus statement as an unpleasant sensory experience associated with actual or potential tissue injuries or described in such terms. The importance of this definition is that you don't have to see overt major lesions for a person to complain of severe pain. There can be a situation with no overt injury, at least in our current limited state of assessment, that can be responsible for severe pain.

  • Pain: Definition

    Slide 11.

    Pain: Definition

    (Enlarge Slide)
  • This is a better definition; it comes from the US Social Security Administration, and it describes pain as a complex experience. So we've taken it out of the realm of a simple neurologic function -- it embraces physical, mental, social, and behavioral processes. It's not just an injury to the bone; it's not just an injury to the nerve. There is something else that is involving the entire person, and when these things come together, they compromise the quality of life of many of our patients. It's this compromised quality of life that ultimately leads patients to suicidality.

  • Pain: Definition (cont'd)

    Slide 12.

    Pain: Definition (cont'd)

    (Enlarge Slide)

Second Evolutionary Step: A Better Understanding of the Physiology of Nociception and Pain Perception

  • The second evolutionary step is a much better understanding of the physiology of pain. I showed you this a little bit before; pain begins at its core in most situations with nociception, which is peripheral nerves functioning to perceive or transduce a thermal, mechanical, or some other type of injury to the system.

  • Pain: A Conceptual Approach

    Slide 13.

    Pain: A Conceptual Approach

    (Enlarge Slide)
  • Much better understood now over the last 2 decades is the impact of a variety of peripheral chemicals and other phenomena that change the milieu in which nociception is processed.

  • Nociception

    Slide 14.


    (Enlarge Slide)
  • These chemicals have been termed or described by Woolf and Chong as a chemical soup, if you will -- an inflammatory soup that can alter the way peripheral nerves work. Probably the most important of these right now happens to be prostaglandins. Prostaglandins are very important for 2 reasons: first, we know that they are ubiquitous chemicals that not only affect the peripheral nervous system but have a role in the CNS. But they're also important for a second, practical reason -- of all these chemicals, they are perhaps the easiest for us to work with, and we work with them through anti-inflammatory drugs; we can inhibit prostaglandin formation. By affecting prostaglandins, we can certainly affect the way pain, in part, can be perceived more centrally.

    So the sensitizing soup displays a phenomenon that changes the way peripheral nociceptors work, altering the sensitivity of those cells.

    Let's look at a simple, common example. If my left hand is sunburned and I tap it and my right hand is not sunburned and I slap it, there's an entirely different sensory experience behind that. And that sensory experience is a phenomenon peripherally mediated through the sensitizing soup, so it changes the way peripheral nociceptors work. Sometimes that peripheral heightening can be permanent.

  • Peripheral Sensitization

    Slide 15.

    Peripheral Sensitization

    (Enlarge Slide)
  • Pain perception occurs when that signal is brought into the nervous system and is either dampened or enhanced by what's going on within the CNS. One used to think of the CNS as being a hard-wired, concrete, simple switching station. We now recognize it to be an infinitely more complex ballet of inhibition and facilitation based upon the status of the posterior horn.

  • Pain: A Conceptual Approach

    Slide 16.

    Pain: A Conceptual Approach

    (Enlarge Slide)
  • If we look at this model, with peripheral nociceptor input, there can be an activity or dose-dependent amount of excitability of the posterior horn. Depending upon what's going on surrounding that horn, the response can be affected, leading to a heightened sensitivity or a heightened perception. What this does is shift, if you will, the dose response curve to the left. We all are familiar with the "shifting to the left" concept; well, a similar phenomenon occurs with pain. For example, let's say we're back in college and we're doing physiology studies for extra money. If the investigator takes a thermal probe at about 80 degrees, we may start to notice it. At about 90 degrees, we might say: "Yeah, that's getting a little uncomfortable." At 105 degrees, half of us will say that it's painful. By the time we get up to 130 or 140 degrees, most of us might say that it's very uncomfortable.

    What has happened over the last 2 decades is a much better understanding of 2 phenomena -- hyperalgesia and allodynia. Hyperalgesia occurs when a normal painful stimulus is perceived as a much more painful phenomenon than it should be: for example, the sunburn. You slap the nonsunburned hand; it has one amount of pain. You slap the sunburned hand and you've shifted that sensitivity to the left so it hurts that much more. Allodynia is the association of a nonpainful stimulus with pain. Most often we see this in neuropathic pain, complex regional pain, or reflex sympathetic dystrophy (RSD) or postherpetic neuralgia. You gently stroke the area that's involved and observe the patient's response. There can be a summation where eventually the patient will withdraw because that nonpainful stimulus is perceived as painful.

  • Central Sensitization

    Slide 17.

    Central Sensitization

    (Enlarge Slide)
  • What does this have to do with anything? There is now a neurophysiologic construct that articulates some of what is going on in the experiences of our patients, things that previously we had not been able to describe. And what do clinicians typically do when they don't have a firm grasp of something? They deny it exists: I don't see it; therefore, it isn't real. And that's the great problem that's faced many of our patients in pain, that they have injuries that we cannot really put our fingers on. But now we have a neurologic model that helps us understand where their pain is coming from, why it might spread, and why it might become more intense over time. What we've typically blamed on malingering and psychiatric disorders may have been a phenomenon within the nervous system.

  • What Does This Mean?

    Slide 18.

    What Does This Mean?

    (Enlarge Slide)

Third Evolutionary Step: A Better Understanding of Pain and Its Impact on Quality of Life

  • The third evolutionary step is really understanding what pain does to us as people. Milton, in the 1600s, wrote in Paradise Lost: "Pain is perfect misery, the worst of evils, and excessive, overturns all patience." We always use the term "pain" to describe something bad or wrong and that's because it's a nice extension from the physiologic to the existential. Untreated physical pain is enough to cause patients to have significant psychologic and emotional decay.

  •  Pain: Definition

    Slide 19.

    Pain: Definition

    (Enlarge Slide)
  • This brings us to the notion of suffering. Pain is not inherently an evil thing; without pain, we would succumb to infection as children. The lack of pain in patients with diabetes contributes to the loss of limbs because wounds and infections don't heal over time. Pain is the most primitive, most protective function of the nervous system.

  • Pain: A Conceptual Approach

    Slide 20.

    Pain: A Conceptual Approach

    (Enlarge Slide)
  • But when pain becomes excessive or continuous, or when it becomes associated with a negative meaning, that is a different situation. If I wake up with back pain, that means I may not be able to play golf or jump on the trampoline with my kids. But if a person who has multiple myeloma that's thought to be in remission wakes up with severe back pain, an entirely different message is sent to that individual. When pain is associated with physical disability or it has social impact or financial impact, we're much more likely to see an association of suffering with it. Suffering is not just the feeling of pain; it is pain that brings with it a negative context.

  • Pain and Suffering Are Not the Same

    Slide 21.

    Pain and Suffering Are Not the Same

    (Enlarge Slide)
  • Becker did a fascinating study that was published several years ago in the Journal of Pain, and what they looked at were patients in an ambulatory and an inpatient pain setting. Using the Short Form (SF)-36, which I'm sure some of you are aware of -- it is a multidimensional quality-of-life assessment tool -- they compared patients suffering from chronic pain with hospitalized patients with chronic obstructive pulmonary disease (COPD), ambulatory patients with renal disease who were receiving dialysis, and patients in a phase IV cardiac rehabilitation program. What they found was that when they looked at self-reports -- not what the clinicians thought, but patient self-reports of quality of life -- individuals with chronic pain viewed their lives as having less quality than patients with COPD and congestive heart failure patients on oxygen or people who had to go for dialysis 3 times a week. So that tells you where these patients are coming from. This is part of the disconnect that we often see when interviewing patients who have chronic pain.

  • Pain and Quality of Life

    Slide 22.

    Pain and Quality of Life

    (Enlarge Slide)
  • Chronic pain leads patients to suicidality. I became interested in this when, in a single day, I had 3 patients try to kill themselves. I looked up the literature on suicide and pain out of my own desperation. This occurred in a setting of intense psychologic support, pharmacologic management of the pain, and rehabilitative interventions. But 3 patients within a 24-hour period all tried to kill themselves. Interestingly, none of them would do it with their medicines; they all took different approaches. The most interesting study here is from Hinkley and Jaremko, published about 10 years ago. These were not psychiatrists, psychologists, or pain doctors; rather, they were managed care medical directors who were trying to understand why this single population of patients, meaning pain patients, had such a high psychological benefit correlated with suicidality and suicidal ideation. So pain drives people to the brink and to extremes.

  • Chronic Pain and Suicidality

    Slide 23.

    Chronic Pain and Suicidality

    (Enlarge Slide)

Fourth Evolutionary Step: A Better Understanding of Pain Characteristics and Pharmacology

  • The fourth evolutionary step is really a much better understanding of characteristics of pain and how we can approach it with medicines. In the 1950s, the English hospice movement taught us that if you dosed patients on an every 2-3 hour basis around the clock, pain levels were reduced, functional status improved, and overall consumption of opioids was reduced. In the 1980s, the phenomenon of incomplete cross-tolerance started to be recognized. Why is it that if I give a person 1 mg morphine and then .5 mg oxycodone, he or she has a fine transition, but another person would either go into withdrawal or become too sedated? Researchers started looking at the genetics of opioid receptors and why each person might respond to a different dose. Then there were the pharmacologic developments from the late 1980s to the present day such as the development of sustained-release opioids, cyclooxygenase-2 (COX-2) drugs, and combination agents like tramadol, as well as novel delivery systems such as oral transmucosal fentanyl citrate.

  • Evolution in Pharmacologic Theory and Technology

    Slide 24.

    Evolution in Pharmacologic Theory and Technology

    (Enlarge Slide)
  • An area of extreme interest is the notion of pharmacogenomics. Pharmacogenomics looks at what genetic influences an individual might have, leading him or her to have different sensitivity to different medications. There are 3 types of opioid receptors: mu, kappa, and delta. Most of our analgesic efficacy comes from the mu receptor, though there is some associated with delta and some side effects are putatively associated with kappa. I learned last week from one of the lead researchers in this area that there are now about 23 different genetic variants of the mu receptor that have been cloned or identified in genomes. A leading pain doctor figures that many more of these will ultimately be identified. Clinically, what relevance does this have? The relevance is that from person to person, even though we all have mu receptors, responses to different opioids will vary. You may have a family of people come in and tell you that the only drug that ever worked was this hydrocodone drug or this oxycodone drug. You'll have tried them on several different medicines, not believing them, thinking that all they're looking for is their drug of choice or drug of abuse. But what they're really looking for is that drug that is going to work best for them with the least amount of side effects. How important is this concept? In a study done by Foley and Hood, 80% of the population responded to whatever drug was given with reasonable and tolerable side effects, while 1 in 5 patients required at least 3 or 4 rotations before coming up with the ideal drug for that individual. So if at first you don't succeed, try again to balance analgesia with side effects.

  • Pharmacogenomics

    Slide 25.


    (Enlarge Slide)
  • Another outcropping of pharmacogenomics is the notion of a dose-response window. The goal for all of us when treating our patients -- whether analgesia, hypertension, or diabetes control -- is to hit the sweet spot with medication, to minimize side effects and toxicity by keeping as low a concentration as possible, but not allowing a symptom or a problem to emerge by having too low a concentration. An old paper on Demerol (meperidine) published back in the 1980s suggested that in a single population of same-age patients given the same kind of surgery, you're going to have a 3-fold dosage difference before you get optimal analgesia between person A and person C. So there is no such thing as a standard dose of pain medicine. The person who comes into the ER and is given 5 mg morphine may have only needed 2 mg, and the next person may need 10 mg to get the same amount of pain relief. Most likely that's a pharmacogenomic phenomenon.

  • Dose Response: The Therapeutic Window

    Slide 26.

    Dose Response: The Therapeutic Window

    (Enlarge Slide)
  • The advent of long-acting opioids has helped provide patients with a level of convenience by not having to dose themselves every 2 to 3 hours with analgesics; it allows us to have better, more consistent serum levels of a medication; and it avoids mini withdrawals. If you tell a patient to take a drug 5 times a day and that drug has a half-life of 4 hours, there's a chance that for several hours at night, they are not going to have any medicine in their system and could potentially go through withdrawal. The idea that there are drugs that you use once a day, twice a day or once every 3 days is very helpful for our patients; it improves adherence tremendously. It's associated with greater patient satisfaction, and actually there are functional data, at least with transdermal fentanyl (Duragesic), that by using systems such as a 3-day patch, you can improve functional outcomes in back pain.

  • Advantages of Long-Acting Opioids

    Slide 27.

    Advantages of Long-Acting Opioids

    (Enlarge Slide)

A Better Understanding of Pain and Its Components

  • What about understanding pain itself? One of the interesting notions is that pain treatment has to stay within a certain level, and this corresponds with the idea that pain stays within the same level. That's not really the case. Throughout the course of the day, the typical cancer patient has anywhere from 4 to 5 spikes of pain above and beyond their background baseline pain. We call this "breakthrough pain." What we're seeing in noncancer pain patients is that the number of these spikes is directly related to the activity level of an individual. If the level of medicine needed to cover baseline pain causes side effects, we may not have as broad a therapeutic window. It can sometimes be difficult titrating our patients to get the right level of analgesia. Fortunately, there is a drug delivery system now available to us that mimics much of these curves for patients; it's a rapid-onset medication, oral transmucosal fentanyl. We've used it guardedly in some patients with noncancer pain who have sudden spikes of this breakthrough pain that we can't control with traditional short-acting opioids.

  • Components of Moderate-to-Severe Chronic Cancer Pain

    Slide 28.

    Components of Moderate-to-Severe Chronic Cancer Pain

    (Enlarge Slide)
  • In cancer pain, you can identify those breakthrough spikes in 1 of 3 ways. Incident pain is pain that occurs when somebody does something. Idiopathic or spontaneous pain is just what it sounds like: it comes out of the blue; there's no way to predict it. A typical example of that might be a tic in a patient with tic douloureux. Then there are patients who have what's known as end-of-dose failure. You give somebody a particular dose of a sustained-release opioid and instead of it lasting 12 hours, it's only lasting 7 hours, so they start to see a gradual buildup in their pain as the dose begins to fail. A history of what the patient's pain experience is like, related to understanding of the pharmacology of certain drugs and the pharmacodynamics of some of these delivery systems, will help you know whether this is dose failure or incident pain. We have collected data on about 1100 patients with noncancer pain. We don't have enough to say how much of this is incident vs end-of-dose failure; that data study is still in process.

  • Types of Breakthrough Pain

    Slide 29.

    Types of Breakthrough Pain

    (Enlarge Slide)

Therapeutic Options and Management Paradigms

  • The statement on this slide is from the US Drug Enforcement Agency; it was published in 2001 and states one of the things that we need to keep in mind is there's a critical balancing act in treating patients. That balancing act hovers between doing the best thing for our patients while at the same time knowing that all of these drugs are subject to abuse and diversion. Through good histories, good physicals, and knowing our patients, we can avoid most of the potential pitfalls. You're the primary care physicians; you know your patients much better than I. We don't advertise; we don't take walk-in patients. Anybody who comes into my office has to be referred by a colleague, much the same way somebody just doesn't walk into a cardiothoracic surgeon's office and say, "You know, I think I need a bypass." At least in our model, patients with pain need to be referred by physicians or by a family member.

  • Promoting Pain Relief and Preventing Abuse of Pain Medications: A Critical Balancing Act

    Slide 30.

    Promoting Pain Relief and Preventing Abuse of Pain Medications: A Critical Balancing Act

    (Enlarge Slide)
  • What are we looking for with our patients? We're trying to maximize function; we're trying to reduce pain. I can make anybody pain-free, but how functional would they be if I had to intubate them? And if we can do these things, then we can really get to the core issue that bothers our patients most, which is that lost quality of life, that disintegration. We don't want to make our patients more disabled by adding a medication; that's what happens to drug addicts: when you add narcotics, you make them more disabled. When you add opioids to a pain patient and monitor them properly, you improve their quality of life. We do that through frequent reassessment. I always keep in the back of my mind the oldest law of medicine or at least Western medicine: above all, do no harm.

  • Goal of Therapy

    Slide 31.

    Goal of Therapy

    (Enlarge Slide)
  • The current pain management paradigm goes something like this: A person is injured, gets sent to physical therapy, and is put on an anti-inflammatory drug. If the patient doesn't respond, imaging or electrophysiologic studies are performed and then other therapeutic interventions like epidurals or nerve blocks are done, depending upon the cause of pain. If that doesn't work, then we start looking at more aggressive medicines; we start thinking about opioids, send the patient off to more aggressive subspecialists and think about a more potent opioid. Then the patient ultimately gets sent to see some kind of pain doctor. We think of the notion of balanced analgesia using therapeutic and diagnostic blocks, and then put our patients into a psychodynamic clinical setting to work on their depression, anxiety, and suffering. When none of this works, we then think about doing intrathecal delivery systems or neuroablative procedures.

  • Current Pain Management Paradigm

    Slide 32.

    Current Pain Management Paradigm

    (Enlarge Slide)
  • What has been suggested by Bennett at the University of Colorado is that perhaps we should start thinking in a different context, where we start offering patients, as soon as possible, the notion of cognitive and behavioral therapies: we discuss alternative medicines, we introduce meditation and prayer. Because these patients get so depressed and anxious; maybe we bring medications and neuromodulation in a little bit sooner. We use pumps and simulators as a last recourse.

  • Revised Pain Medicine Paradigm

    Slide 33.

    Revised Pain Medicine Paradigm

    (Enlarge Slide)

Balanced Analgesia With Other Therapeutic Options

  • The whole goal of trying to treat patients with medications is a balanced analgesic; there is no such thing as a single silver bullet that is going to take care of all pain problems. If there is, then somebody's hiding it!

  • Balanced Analgesia in the Treatment of Pain

    Slide 34.

    Balanced Analgesia in the Treatment of Pain

    (Enlarge Slide)
  • We usually have to think of the dorsal horn and the periphery when considering what medicines we can use that will work across this polyglot of receptors to try and improve pain and settle down angry spinal cords. This is pharmacosynergy; to walk you through it, we would use prostaglandin-inhibiting agents to produce an effect further downstream, but there's also some prostaglandin activity at this level. There's a variety of medicines ranging from opioids to clonidine that we can implement to get patients' pain under better control.

  • Nociception and Synergism

    Slide 35.

    Nociception and Synergism

    (Enlarge Slide)
  • But it's not just about medicines; rehabilitation is key. If somebody's been disabled with pain, I guarantee they'll be cardiovascularly and musculoskeletally deconditioned. Physical therapy is not going to cure anybody's pain, but if we use the rehabilitation model from, say, neurologic rehabilitation, it will improve an individual's ability to function with what they have. We need to bring in psychologic therapies, be they cognitive, behavioral, or psychiatric, and then use our interventional approaches judiciously. But no single modality done in isolation is going to be enough for an individual with chronic pain.

  • Therapeutic Options

    Slide 36.

    Therapeutic Options

    (Enlarge Slide)
  • A number of medicines are available, including everything from tricyclics to newer antidepressants.

  • Adjuvant Analgesics

    Slide 37.

    Adjuvant Analgesics

    (Enlarge Slide)

Multidisciplinary Programs

  • We want to use multidisciplinary programs; Boston has one of the best in the world at Spaulding Rehabilitation Hospital. We send patients up there occasionally to do inpatient pain management. The goal of these programs is to try to maximize function, reduce medication levels, and improve psychologic strength to deal with an ongoing pain problem.

  • Multidisciplinary Programs

    Slide 38.

    Multidisciplinary Programs

    (Enlarge Slide)
  • There are a number of interventional therapies. The future of much of what we do is listed here, with intrathecal pumps being able to deliver more potent targeted pharmacotherapeutics right to the source of pain and pain modulation. But in many of our offices, just simple trigger points can help alleviate back pain, neck pain, and shoulder pain.

  • Interventional Techniques

    Slide 39.

    Interventional Techniques

    (Enlarge Slide)


  • When it comes to opioids, they still remain controversial. There remains a fear among practitioners about injudicious scrutiny: will I lose my license? Am I going to have Big Brother knocking down my door? We worry about getting scammed as well by our patients; we don't want to be contributors to a problem in our community. In recent years, a number of professional societies have advocated better and more consistent use of opioids across a number of disease spectrums.

  • Opioid Analgesics

    Slide 40.

    Opioid Analgesics

    (Enlarge Slide)
  • There is no such thing as a perfect opioid. Up until recently, we've only had 3 long-acting opioid molecules available to us; within the near future, we're going to have another 2 put into our armamentarium. When we're treating patients with opioids, like any other medicine, we pretreat likely side effects. Every person who gets an opioid is going to become constipated. So pretreat it; the last thing you want to do is to have to meet your patients in the emergency room because they're impacted.

    Patients are going to respond differently to different drugs, so just because someone doesn't respond the way you think, it doesn't mean they're trying to pull the wool over your eyes. The best consult I ever had was, "Please evaluate this patient; he knows too much about narcotics." He knew too much about narcotics because he was a sickle cell anemia patient, a "sickler," who had moved to Connecticut from California and had been tried on every opioid in the world at the Scripps Clinic. Imagine if somebody walks in to the ER and says: "I'm about to go into a sickler crisis, could you give me 2 L of fluid and some intravenous morphine and I'll be okay in a couple of hours." This patient knew his disease and he knew how to be treated, much to the skepticism of our hospital.

    I took hydrocodone after having knee surgery and it gave me great pain relief; I couldn't fall asleep for days on end. I took oxycodone; it gave me great pain relief and I couldn't wake up. These are structurally 99.9% the same drug. So sequential trials are important; you want to make sure you try drugs and monitor patients for effects and side effects.

  • Opioid Selection

    Slide 41.

    Opioid Selection

    (Enlarge Slide)
  • When you're prescribing an opioid, follow some procedures: Document function; document analgesia; document outcome. And when needed, seek consultation. Don't be afraid to ask for help when you need it.

  • Summary: Opioid Prescribing Principles

    Slide 42.

    Summary: Opioid Prescribing Principles

    (Enlarge Slide)
  • There are several pure opioid agonists available; the best thing about them is that you can push doses to efficacy.

  • Pure Opioid Agonists

    Slide 43.

    Pure Opioid Agonists

    (Enlarge Slide)


  • Earlier, I discussed the notion of pain being a series of processes that affect the entire individual. When we're trying to be rational about treating our patients, we want to think in terms of something like this, that we want to minimize input from nociceptors. If it's a knee, let's put some cortisone in there, let's put some Synvisc (hylan G-F 20) in there, let's brace it, strengthen the quads, and use anti-inflammatories. If the pain is starting to become really problematic, how can we modify the effect that this nociceptor is having on the spinal cord and the CNS? If we're really starting to see suffering because a person's losing quality of life, we want to address it aggressively, both pharmacologically and nonpharmacologically. And then if somebody really starts experiencing or expressing pain behaviors, especially the injured worker or the person that you're concerned about withdrawing from his or her family, seek out and put into effect a multidisciplinary program that includes cognitive therapies.

  • Pain: A Conceptual Approach to Treatment

    Slide 44.

    Pain: A Conceptual Approach to Treatment

    (Enlarge Slide)
  • I'm going to finish with just a couple of quick points. Pain is a complex experience -- no simple, single therapy is going to work for the majority of our patients, at least at the outset. Locally directed therapies can have an effect, but really you need to think globally and not locally. Opioids are an important part of the recipe, but they're not the only part. We should be prescribing opioids with the same care you would with a potent cardiovascular agent or with something as toxic as insulin. You want to monitor your patients; you want to use opioids as part of an intradisciplinary approach, not just as monotherapy.

  • Comprehensive Approaches to Treatment: Palliative Not Curative

    Slide 45.

    Comprehensive Approaches to Treatment: Palliative Not Curative

    (Enlarge Slide)
  • I'll finish with this. For people who suffer with pain, it's really terrible. They feel that no one believes them -- their doctors chief among them -- that their lives have been taken from them for some reason, whether it's because they've had inappropriate spinal surgery or they've had some kind of an accident; and they've just watched their lives get sucked away from them. We can offer so much now for that population through a skillful, cognitive, nonjudgmental approach. And that's why I love this quote from the book Les Miserables: "Would you realize what revolution is, call it progress; and would you realize what progress is, call it tomorrow."

  • What Is Revolution?

    Slide 46.

    What Is Revolution?

    (Enlarge Slide)