Managing Pain

Pain.

Little scares a new oncology patient as much as the idea of pain.  Unfortunately, pain permeates my practice.  Often, pain is the initial symptom that leads to a new cancer diagnosis.  Cancer patients undergo frequent painful procedures -- biopsies, bone marrow aspirates, surgeries ... even a simple blood draw involves a small amount of pain.  Because of this, managing pain is something I have some experience doing.

So I was surprised when I read this article in The Washington Post this morning and discovered that "some [pain doctors] began decrying the increasingly widespread use of opioids and questioned whether the drugs worked."  Really?  There are pain doctors who question whether opiates (morphine, for example) work?

Over the years, I have seen a variety of pain management styles. From doctors who prescribe intramuscular injections of pain medications to small children recovering from surgery, through sophisticated regimens involving patient-controlled analgesia and the use of non-drug techniques designed to specifically combat different types of pain. Pain management skills vary widely, and careful use of appropriate therapies can make all the difference to a suffering child.

Unfortunately, because the drugs which are the mainstay of pain treatment, opiates, are highly addictive, their use is politicized.  The article in today's Washington Post, for example, was focused on a patient advocacy group, the American Pain Foundation, which gets the lion's share of its funding from the pharmaceutical industry.  Unfortunately, this creates the appearance of a conflict of interest when the group strongly advocates for the use of specific narcotic pain medications (such as OxyContin) to control chronic pain.  And the appearance of a conflict of interest, whether or not the conflict exists, is sufficient to cast doubt on everything the Foundation has to say, even when what they say is spot on.

The use of narcotic pain medications is clearly expanding, and as a result, overdoses are an increasingly common cause of death in this country.  That doesn't mean these drugs should not be used.  They are highly effective at controlling acute, and even chronic, pain.  But like all medications, they need to be used appropriately, under medical supervision, prescribed by doctors who are experienced in their use, know how they work, know what kinds of pain they help, and know the risks and limitations of their use.

The diseases I treat cause pain.  One of the most common fears among cancer patients is the fear of dying in pain.  The treatments I use cause pain.  Some of the procedures we perform to monitor the progress of my patients cause pain.  Without highly effective drugs to treat pain, I could not do my job.  Rather than politicizing these drugs, we should be advocating for increased education about their proper use, about choosing the right drug for the right type of pain, and increasing research into the mechanisms of pain so that newer, more effective, safer drugs can be developed.

Photo Credit

Related Posts:
What Rufus Can Teach Us About Pain
Fentanyl Revisited
Narcotics for pain control:  When is enough too much?

What Rufus (The Naked Mole Rat) Can Teach Us About Pain

On December 25, I posted a piece about pain management and the role of strong narcotics such as fentanyl. One of the points I wanted to make was that there are different types of pain, primarily neuropathic pain and inflammatory pain. In managing patients with cancer pain (or any type of chronic pain, for that matter), it is critical to distinguish between these types of pain, because they respond to different classes of drugs. A paper published today in an online peer-reviewed journal called PLoS Biology reports that a particular animal is insensitive to inflammatory pain.

What animal, you ask? The African naked mole-rat (Heterocephalus glaber).

It turns out that naked mole-rats do not have the pain-related neuropeptide Substance P in the nerves in their skin, which means they cannot feel any inflammatory pain. Scientists tested this in a variety of ways, including injecting very small amounts of either dilute acid (about the strength of lemon juice) or capsaicin (the substance that makes hot peppers “hot”) into their paws. They did not react. To prove that Substance P is necessary and sufficient for the animals to feel pain, the scientists replaced the gene for Substance P in the nerves to one paw, leaving the other 3 alone. In animals treated in this way, injections of capsaicin into the paw with Substance P caused the animals to withdraw and lick their paws, while the mole-rats did not respond to injections into the other 3 paws.

Why is this an important experiment? According to the lead author on the study, "This is important specifically to the long-term, secondary-order inflammatory pain. It's the pain that can last for hours or days when you pull a muscle or have a surgical procedure…We're learning which nerve fibers are important for which kinds of pain, so we'll be able to develop new strategies and targets." Added his supervisor, "We really do not understand the molecular mechanism of acid sensing in humans, although it is thought to be pretty important in inflammatory pain. An animal that naturally lacks such a mechanism may help us identify what the mechanism actually is."

What else do we know about naked mole-rats? Well, these fascinating creatures live in oxygen-starved burrows 6 feet under the ground in East Africa. They are the only cold-blooded mammals. And… some of them can become martial arts masters.



Also, naked mole-rats are an important tool in the study of human aging.

In all seriousness, this is just another example of how science, driven only by curiosity (and not by policy), can lead to unexpected, yet fascinating and ultimately extremely important findings. The best example of that is the discovery of bacteria that live in heated vents on the ocean floor. These bacteria are the original source of the heat-stable Taq DNA polymerase, without which PCR (one of the most important laboratory techniques in molecular biology today) would be impossible.

So the next time you hear about research that on its surface sounds silly, please try to keep an open mind, knowing that important findings sometimes come from the most unexpected places.

I leave you with that thought, and this song:

Fentanyl Revisited

One of my most faithful readers, Elizabeth Munroz, suggested that I expand on my discussion from my last blog entry about pain management and the role of fentanyl. I think that’s an excellent idea, because this is a topic I feel very strongly about.

A computerized search of the medical literature (http://www.ncbi.nlm.nih.gov/sites/entrez/) for articles about chronic pain turned up 45,290 articles. Clearly this is a topic of intense research, and my goal here is not to write a textbook, but rather to touch on the highlights of pain management in the cancer patient, so that articles in the popular press about pain medications can be read in this context.

Acute vs. Chronic Pain

One of the points I made, and one of the concerns raised by the FDA in their recent warnings regarding fentanyl patches, is the difference between acute and chronic pain. At its simplest, the difference is obvious: acute pain happens suddenly (think of your last headache) and eventually goes away, while chronic pain lasts a long time (like someone with a bad back, whose back hurts every single day). But upon a closer look, these differences become less distinct. Someone with a bad back might have pain every day, but if they try to lift something heavy, that can send a sharp spasm of significantly increased pain shooting through them. Is that acute pain? Actually, for people who have pain every day, we usually think in terms of chronic pain with acute exacerbations. This acute jolt of pain takes place on the background of the daily pain… an important distinction for treatment.

Different Types of Pain

Pain can not only be acute or chronic, but there are different types, one of the most important being neuropathic. Imagine the pain that comes from bumping into a bruise on your thigh. Now imagine the pain that you feel when your leg has “fallen asleep.” The first of these is what pain management doctors call “nociceptive pain” and arises from tissue damage or inflammation, and the second is “neuropathic pain” and arises from damage to a nerve. Biologists have learned that these different types of pain are transmitted through different types of nerves and using different molecular mechanisms. Doctors have learned that these biological differences mean that the management of these different types of pains requires different strategies.

How do we feel pain?

There actually is no easy answer to this seemingly simple question. However, scientists do understand to some extent. When there is damage to tissue (such as from trauma or inflammation), nerves sense this damage, fire a signal to the brain, and the brain interprets this signal as pain. There are proteins in the brain called opiate receptors. These proteins help determine how active certain nerves are – the nerves that mediate the sensation of pain. Your body makes substances that attach to opiate receptors and turn down the activity of the pain-sensing nerves, decreasing the sensation of pain.

How do pain medicines work?

Opiate receptors are the targets of narcotic pain medicines, like morphine and fentanyl. The medicine attaches to the opiate receptor and turns down the activity of the nerve. Inflammation is the target of most over the counter pain medications, like ibuprofen. Less inflammation means less tissue damage, which means less activity of the nerve, and less pain. Neuropathic pain arises from damage to nerves, and medicines like neurontin help treat neuropathic pain by directly turning down the activity of the damaged nerve. These differences are very important, because the different types of pain have different causes and need different medicines to treat them.


Courtesy of NIAAA
The figure shows how some nerves make opioids (endorphins) that send a signal to other nerves. Narcotics (exogenous opiates) mimic this signal, turning down the activity of a nerve involved in sensing pain. Naltrexone is a drug that blocks the action of opiates by blocking their ability to attach to the opiate receptor.

How are narcotics different from each other?

All narcotics work basically the same way – they attach to the opiate receptor. So what’s the difference between morphine and fentanyl? The major differences relate to how the drug is handled by the body. Fentanyl attaches much more tightly to the opiate receptors than morphine, so you need much less drug to ease the same amount of pain (in fact, fentanyl is about 100 times more potent than morphine). But fentanyl doesn’t last as long in the body. A dose of morphine can kill pain for 4-6 hours, compared to only an hour or so for a single dose of IV fentanyl. This short duration is the reason for the development of fentanyl patches… by slowly releasing the drug into the body, it can be made to last much longer. A fentanyl patch can provide pain relief for days at a time.

What about tolerance?

In an earlier article, I talked about the difference between tolerance and addiction. How does tolerance happen? Well, if the opiate receptors all have narcotic attached to them, the nerve senses this and makes more receptor. Now there are new opiate receptors that are not bound up with narcotic, and the pain comes back. With more opiate receptors on the nerve, a higher narcotic dose is needed to turn off the nerve’s activity. We call this tolerance. This happens to every chronic pain patient. They need to take more medicine to experience the same degree of pain relief. This isn’t a character flaw, and it isn’t addiction. It’s the body’s response to being treated with the drug every day.

Tolerance is exactly why fentanyl patches are meant for chronic pain and not acute pain, and why putting on a fentanyl patch for a headache can lead to an overdose. Fentanyl, being so potent, rapidly saturates the opioid receptors on the nerves of patients who don’t take these medications every day.

Pain management strategies for the chronic pain patient

So how do I treat pain in my patients? The first step is to try to determine the type of pain, so that I’m using the right drugs. If the patient has neuropathic pain, morphine won’t work as well as neurontin. If the patient has chronic pain, they need something long lasting, like a fentanyl patch or methadone. But even chronic pain patients have acute pain episodes on top of their chronic pain. For these acute pain episodes, the patient needs something that will work quickly to relieve the pain fast, but won’t last too long, so that when the pain is gone, so is the medication. Oxycodone is perfect for that type of pain: it starts to work in minutes and only lasts a few hours (unlike the sustained release version, oxycontin, which takes an hour to kick in and lasts for 8-12 hours).

Some final thoughts

Pain is manageable. The key to helping a cancer patient with their pain is to understand the different types of pain, why some medications work for some kinds of pain but not others, and to work hard to balance the benefits of pain medications with the side effects in order to maximize the quality of the patient’s life. Thankfully, here in the US, we have an abundance of pain medications available, and no one needs to live in pain for lack of taking pain medications (which is not the same thing as saying no one needs to live in pain, because unfortunately, we can’t relieve all pain). Fentanyl is a potent drug, but it’s the misuse of fentanyl that the FDA is warning about, not the correct use. Used properly, fentanyl is (in Elizabeth’s words) “a godsend” for patients with chronic pain. It shouldn’t be taken off the market, it should be used correctly.

Breaking News: the FDA (re)issues warning about fentanyl

In September, I wrote about the double-edged sword of narcotics and pain control for cancer patients. Around that same time, there were news reports of patients dying from improperly prescribed Fentora, which is a preparation of the powerful narcotic, fentanyl, that is absorbed through the lining of the mouth.

Fentanyl is in the news again this week. This time, the issue is with fentanyl patches. These are a favorite tool for oncologists, because the drug is absorbed through the skin. This means the patient need not swallow a pill, a big deal for patients receiving chemotherapy (notorious for causing nausea and vomiting). Fentanyl patches are also great for managing chronic pain in patients who have significant prior narcotic exposure, and it’s hard to imagine practicing oncology in the US without this tool.

However, like all tools, improper use can result in great harm.

At a news conference last week, the FDA reissued a 2-year-old warning about fentanyl patches, which have been linked to at least 120 deaths. They repeated their advice that these patches be reserved for patients with chronic pain and a tolerance to opioids. The patients who have died have all been prescribed for acute pain (in one case, a headache) and had never taken narcotics before.

Fortunately, the FDA does not seem likely to heed the call from some people to limit the ability to prescribe fentanyl patches to pain specialists. This would be a big mistake, because there are only 4,000 pain medicine specialists in the US, and many, many patients with chronic pain are treated safely and effectively by experienced physicians without specific pain training.

Bottom line? Pain medicines are powerful medicines. Used incorrectly, these medications can be deadly. But, used correctly, they can make life tolerable for people who would otherwise suffer terribly. That fact alone is sufficient to keep them on the market, and in the hands of doctors who know how to use them and patients who need them.

Narcotics for pain control: When is enough too much?

Ask 100 cancer patients what they fear most, and I’m sure almost all will say the same thing: pain. What do people think of when they think about cancer? Pain. So what is one of the most important things I can do for my patients? Control their pain.

There are many ways to control pain. Sometimes, when the medicines we use to treat cancer shrink the size of the tumor, the pain is eased as well. Sometimes medicines that are approved by the FDA for treating pain can also treat the cancer. A great example of this is Quadramet, an injectible radioactive drug, approved to treat bone pain in patients whose breast or prostate cancer has spread to bones, that we are using in a clinical trial to treat bone cancer, osteosarcoma.

Much more common, though, is the use of narcotics to treat cancer pain. But like almost every medicine, these drugs come with side effects. Feared ones. The two biggest fears among patients? That they may become addicted or they may die.

Let’s talk about addiction.

I’ll tell you about my patient, Q (not her real initial, given the sensitive nature of her story). When Q was diagnosed with osteosarcoma, the cancer had already spread throughout her lungs. She completed the usual course of chemotherapy and had a major operation to remove the tumor in her leg, but when it was all done, she was in pain and still had cancer in her lungs. Throughout her course, we were giving her oxycodone and OxyContin to control her terrible pain. After experimental treatment and truly heroic lung surgeries, however, she achieved a remission.

But as the pain lingered on, so did the use of oxycodone and OxyContin.

Soon she experienced one of the problems most narcotic patients go through – tolerance. She needed more and more medicine to achieve the same degree of pain control, because her body “got used to” the drugs.

Next she experienced another of the common problems with narcotics – dependence. Her body got so used to the drugs that attempts to take them away caused symptoms: sneezing and yawning weren’t so bad, but chills and diarrhea and pain? Those were terrible. So to ward them off, she took more painkillers.

Tolerance and dependence are normal reactions of a normal healthy body to chronic narcotic use. Tolerance and dependence are not the same as the dreaded “A” word – addiction.

Most people who use narcotics correctly never get addicted. Unfortunately, Q became addicted. Addiction is a psychological dependence on the drug… a strong feeling of NEEDING the drug. Dependence and tolerance are biological, they relate to how the body processes the drug, and can be easily managed. Addiction is an altogether different matter. Managing and dealing with addiction is NOT easy for either the person addicted or for their family members. Recovery from addiction is possible, but it is all too often a long and difficult process.

But imagine a world without pain medicines – a world where people suffer through physical pain without any relief. Awful, isn’t it? Unfortunately, as reported in the New York Times on September 10, 2007, this situation is all too real for many of the world’s poorest people. Their governments, so concerned about protecting people from addiction, have all but banned the use of these drugs. This has left cancer patients, and many others, to die a slow, painful, and horrifying death. They die with a pain that is altogether preventable, but is not because of government fear of addiction.

But addiction is a real danger, even when these drugs are used properly. OxyContin made a big splash when it was introduced, because its manufacturer, Purdue Pharma, claimed that, because it was a slow release formulation, it was not addictive. This is not true, and Purdue Pharma paid a hefty price for misleading physicians and consumers.

Death is also a risk, especially if these drugs are used incorrectly. Within the last two weeks, the Food and Drug Administration issued warnings after several patient deaths were linked to improper use of Fentora, a formulation of a powerful narcotic called Fentanyl, that is absorbed through the lining of the mouth.

So should we fear narcotics? Should they be banned like they are in parts of Sierra Leone (as reported by the New York Times)? Certainly not. No one should have to suffer like this woman.


Photo courtesy of NYTimes.com

But we do need to respect them. These drugs need to be used properly. They need to be used carefully. And patients need to be warned that tolerance and dependence are expected, but that they are NOT signs of addiction.

And we need to remember that addiction is treatable. I just saw Q for a routine follow up appointment 2 weeks ago. After several inpatient detox stays, she has kicked her narcotic habit (she had graduated from OxyContin to heroin) and she was back in college. What an inspiration Q is! First she beat cancer, then she beat addiction. I’m sure she’ll beat whatever other challenges life throws at her on her way to the top!