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.